Radiological imaging of teratological fetuses: what can we learn?

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Boer, Lucas L; Schepens-Franke, A N; van Asten, J J A; Bosboom, D G H; Kamphuis-van Ulzen, K; Kozicz, T L; Ruiter, D J; Oostra, R-J; Klein, W M

2017-06-01

To determine the advantages of radiological imaging of a collection of full-term teratological fetuses in order to increase their scientific and educational value. BACKGROUND : Anatomical museums around the world exhibit full-term teratological fetuses. Unfortunately, these museums are regularly considered as "morbid cabinets". Detailed dysmorphological information concerning the exhibited specimens is often lacking. Moreover, fetuses with severe and complex congenital anomalies are frequently diagnosed incompletely, incorrectly or not at all. In order to verify diagnoses and to enrich their educational and scientific value, we imaged 41 out of the 72 teratological specimens present in the collection of our Anatomy and Pathology Museum in Nijmegen (The Netherlands) by means of magnetic resonance imaging (MRI) and computed tomography (CT). Additionally, contemporary dysmorphological insights and 3D models are implemented in the teratology education of medical students and residents. Full-term teratological fetuses have become increasingly rare and deserve a prominent place in every anatomical museum; they are suitable for contemporary teratological research and education. Modern radiological techniques markedly enhance their scientific and didactic value. • To explore the scientific and educational potential of institutionalised teratological collections • To understand the additional value of radiological imaging in diagnosing teratological specimens • To learn about the specific settings of MRI parameters when scanning fixed specimens • To recognise specific internal dysmorphology in several congenital anomalies.

Holoprosencephaly: A mythologic and teratologic distillate.

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Cohen, M Michael

2010-02-15

This review of holoprosencephaly provides a mythologic and teratologic distillate of the subject under the following headings: Babylonian tablets; Greek mythology; pictures from the 16th through the 20th Centuries; 19th Century teratology; history of more modern concepts and their terminologies; and ocean-going ships named "Cyclops." 2010 Wiley-Liss, Inc.

A mixed model framework for teratology studies.

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Braeken, Johan; Tuerlinckx, Francis

2009-10-01

A mixed model framework is presented to model the characteristic multivariate binary anomaly data as provided in some teratology studies. The key features of the model are the incorporation of covariate effects, a flexible random effects distribution by means of a finite mixture, and the application of copula functions to better account for the relation structure of the anomalies. The framework is motivated by data of the Boston Anticonvulsant Teratogenesis study and offers an integrated approach to investigate substantive questions, concerning general and anomaly-specific exposure effects of covariates, interrelations between anomalies, and objective diagnostic measurement.

Inhalation developmental toxicology studies: Teratology study of tetrahydrofuran in mice and rats: Final report

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Mast, T.J.; Evanoff, J.J.; Stoney, K.H.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

1988-08-01

Tetrahydrofuran (THF), a four-carbon cyclic ether, is widely used as an industrial solvent. Although it has been used in large quantities for many years, few long-term toxicology studies, and no reproductive or developmental studies, have been conducted on THF. This study addresses the potential for THF to cause developmental toxicity in rodents by exposing Sprague-Dawley rats and Swiss (CD-1) mice to 0, 600, 1800, or 5000 ppm tetrahydrofuran (THF) vapors, 6 h/day, 7 dy/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.33 positively mated rats or mice. Positively mated mice were exposed on days 6--17 of gestation (dg), and rats on 6--19 dg. The day of plug or sperm detection was designated as O dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded and live fetuses were examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 27 refs., 6 figs., 23 tabs.

Mini-review: history of organized teratology information services in North America.

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Leen-Mitchell, M; Martinez, L; Gallegos, S; Robertson, J; Carey, J C

2000-04-01

A history of the Organization of Teratology Information Services (OTIS) is presented in context of the history of teratology information services. During the late 1970s, teratology information services grew out of the need for current and accurate information about fetal effects of environmental exposures in pregnancy. Over the next decade, teratology information services networked and collaborated, developing their own professional organization. A description of the activities of OTIS is described. Copyright 2000 Wiley-Liss, Inc.

Teratology in cultural documents and today.

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Schumacher, Gert-Horst

2004-12-01

Teratology is the science of congenital malformations. The incidence of birth defects amounts to 2-3%, but it doubles postnatal owing to the fact that many dysfunctions are not discernible at birth. Congenital malformations were already known in ancient cultures, records from Assyrian and Babylonian astrologists as well as from physicians and philosophers of the Hippocratic era are testifying it. In medieval times they were recognized as supernatural phenomenons, terata, from what the term TERATOLOGY derived. In the eyes of the superstitious people affected stillborns were regarded as monster, symbol of devil or miracle. The foundation of anatomy as a science by Vesalius marked the beginning of a reorientation. In the 17th century, when the age of enlightenment began, ideas concerning the origin of birth defects became more objective. Original studies dealing with congenital malformations became common in the 18th century. Fundamental discoveries made by microscopy placed Teratology on a truly scientific basis. Significant impetus was grown to teratological research with the discovery of Gregg (1941) that German measles (rubella virus) of pregnant women caused birth defects in the embryo and the contergan disaster (1959--1962). Congenital malformations originate from genetic factors (single gene defects and chromosomal aberrations) and environmental factors, such as radiation, drugs, chemicals, and infectious agents. The susceptibility of teratogen depends on the period of embryonal development, which is classified into gametogenesis, blastogenesis, embryogenesis and fetogenesis. The Food and Drug Administration of the USA published guidelines for teratogenetic testing (1966). There are in-vivo and in-vitro-test programmes, the latter became of increasing importance owing to the large number of chemicals to be tested and the activities of opponents against animal experiments. Although great advances were made, the problem remained to transfer results from in

Teratology in Mexico. 19th Century.

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Gorbach, Frida

2014-01-01

It was not until the last third of the 19th century, the period in which, according to historiography, the country definitely inserted itself into modernity, that anomalies and monstrosities had a presence in Mexico. Therefore, what I present here are four moments of teratology in Mexico, four dates in which I try to recount how teratology, which still occupied a marginal place within the main themes of national science, not only reached to cover the realm of medical discussions at the time, but also laid the foundations for new disciplines like biology and anthropology.

The neurobehavioral teratology of retinoids: a 50-year history.

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Adams, Jane

2010-10-01

This review of the central nervous system (CNS) and behavioral teratology of the retinoids over the last 50 years is a commemorative retrospective organized by decade to show the prominent research focus within each period and the most salient findings. In the 1960s, research focused on the gross CNS malformations associated with exposure and the delineation of dose-response and stage-specific responses in rodent models. Relevant scientific events before and during the 1960s are also discussed to provide the zeitgeist in which the field of neurobehavioral teratology emerged in the 1970s. During this period, studies demonstrated that adverse effects on postnatal behavior could be produced in animals exposed to doses of vitamin A lower than those that were teratogenic or impacted growth. Work during the 1980s showed an overrepresentation of behavioral studies focused on the reliability of screening methods, while the marked effects of human exposure were illustrated in children born to women treated with isotretinoin during pregnancy. The human catastrophe invigorated research during the 1990s, a period when technological advances allowed more elegant examinations of the developing CNS, of biochemical, cellular, and molecular developmental events and regulatory actions, and of the effects of direct genetic manipulations. Likewise, research in the 1990s reflected a reinvigoration of research in neurobehavioral teratology evinced in studies that used animal models to try to better understand human vulnerability. These foci continued in the 2000-2010 period while examinations of the role of retinoids in brain development and lifelong functioning became increasingly sophisticated and broader in scope. This review of the work on retinoids also provides a lens on the more general ontogeny of the field of neurobehavioral teratology. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc.

Comments from the Behavioral Teratology Committee of the Japanese Teratology Society on OECD guideline for the testing of chemicals, proposal for a new guideline 426, developmental neurotoxicity study, draft document (September 2003).

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Fukui, Yoshihiro; Ema, Makoto; Fujiwara, Michio; Higuchi, Hashihiro; Inouye, Minoru; Iwase, Takayuki; Kihara, Takahide; Nishimura, Tatsuya; Oi, Akihide; Ooshima, Yojiro; Otani, Hiroki; Shinomiya, Mitsuhiro; Sugioka, Kozo; Yamano, Tsunekazu; Yamashita, Keisuke H; Tanimura, Takashi

2004-09-01

In September 2003, a new revision of the draft guideline (Organization for Economic Co-operation and Development [OECD] Guideline for the Testing of Chemicals, Proposal for a New Guideline 426, Developmental Neurotoxicity Study) was distributed. The draft guideline consists of 51 paragraphs and an appendix. The National Coordinators were requested to arrange national expert reviews of the guideline proposal in their member countries. The member of the Behavioral Teratology (BT) Committee of the Japanese Teratology Society (JTS) reviewed, discussed and commented on the draft Test Guideline proposal. The BT Committee of the JTS also commented that the International Collaborative Study to validate this protocol should be definitely performed. These comments were sent to the OECD Secretariat. The BT Committee of the JTS expects that the comments are useful for further discussion.

New teratological examples in Neotropical Staphylinidae (Insecta: Coleoptera, with a compilation of previous teratological records Nuevos ejemplos teratológicos en Staphylinidae neotropicales (Insecta: Coleoptera, con una compilación de registros teratológicos previos

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Julieta Asiain

2009-04-01

Full Text Available Teratology is the study of malformations that affect various organisms and may cause taxonomic confusion. The goal of this work is to compile the previously published information about malformations in species of Staphylinidae, to describe 10 teratological cases that have not been previously recorded in neotropical species of this family, and to point out the high frequency of these malformations in the studied specimens. The previously recorded cases were obtained from review of 13 papers, and the studied specimens were obtained on loan from several collections. In total, 43 teratological cases were compiled for Staphylinidae, belonging to 39 species from 8 subfamilies. Ten teratological cases are described for specimens from Belonuchus, Agrodes and Plochionocerus. One of them occurs in B. apiciventris, 2 in A. elegans, 3 in P. humeralis, 3 in P. fulgens and 1 in P. splendens. Most of the anomalies affect the antennae (7 cases, but teratologies that affect mandibles (1 case, midlegs (1 case and pronotum (1 case are also presented.Teratología es el estudio de las malformaciones que afectan a distintos organismos y que pueden causar confusiones taxonómicas. El objetivo del presente estudio es recopilar la información previamente publicada sobre teratologías en especies de Staphylinidae, dar a conocer 10 casos de anomalías presentes en especies neotropicales de esta familia que no han sido reportadas con anterioridad, así como resaltar la alta frecuencia de estas deformaciones en los organismos estudiados. Los casos previamente reportados se obtuvieron de la revisión de 13 trabajos, mientras que los ejemplares estudiados proceden del préstamo de organismos de distintas colecciones. Se recopiló un total de 43 casos teratológicos para Staphylinidae, pertenecientes a 39 especies de ocho subfamilias. Se describen 10 casos teratológicos en ejemplares de Agrodes, Plochionocerus y Belonuchus, 2 de ellos se presentaron en A. elegans, 1 en B

Funding for teratology information services: up, down, and all around.

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Quinn, Dee

2012-08-01

Funding for Teratology Information Services has been an ongoing struggle over the 25 years of its existence. Traditional and novel funding mechanisms have been explored with varying success. The importance of providing teratology risk assessment and counseling to all women of reproductive age is now an established health care objective. Sufficient and stable funding for these services is essential. Copyright © 2012 Wiley Periodicals, Inc.

Thomas H. Shepard, M.D., pioneer in embryology and teratology.

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Fantel, Alan G; Polifka, Janine E; Oakley, Godfrey P

2017-06-01

Dr. Thomas H. Shepard died on October 3, 2016 at the age of 93. He was a major figure in the fields of teratology, embryonic and fetal pathology, and pediatrics. He was beloved by his colleagues as he was by the many students and fellows whom he taught, mentored and befriended. His contributions to teratology are extraordinary and he is greatly missed. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Digital data and the 19th century teratology collection

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Baljet, B.; Oostra, R. J.

1999-01-01

The golden age of descriptive teratology (congenital anomalies) was between 1750 and 1850. During that period, the study of human congenital malformations, especially those dramatic examples designated as 'monsters', attracted special attention. One of the finest collections in this field was Museum

A hitchhiker's guide to the older literature of descriptive teratology.

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Beckwith, J Bruce

2007-12-15

Though relatively neglected in the age of molecular biology, the older literature of teratology includes superb illustrations and descriptions of malformations, and other information of permanent value to science and medicine. Accessing that literature can be challenging, as most is in works that are rare, published in languages other than English, and not available in digital form. This article describes some valuable sources of information concerning the antiquarian literature of descriptive teratology. (c) 2007 Wiley-Liss, Inc.

The contribution of new findings and ideas to the old principles of teratology.

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Jelínek, Richard

2005-01-01

Although the last generally accepted concept of principles of teratology was issued more than 30 years ago, the cause of less than 50% of all congenital anomalies is known and no substantial change in their incidence has been observed worldwide. In the meantime, powerful techniques of molecular biology as well as many sophisticated preventive measures have been introduced with marginal effects on the overall birth defects numbers. In this paper, we follow the history of basic concepts of teratology starting with Isidore Geoffroy Saint-Hilaire and Dareste, followed in the 20th century by James Wilson. Since that time no bright and completely new idea, which would deserve the name principle, has emerged. The advanced molecular studies support the long-existing principles and disclose the great variability of individuals and their responses to adverse exposures. In this way, the future of teratology counseling may be seen in a deep analysis of any individual case.

Cost effectiveness of teratology counseling - the Motherisk experience.

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Koren, Gideon; Bozzo, Pina

2014-01-01

While the benefits of evidence-based counseling to large numbers of women and physicians are intuitively evident, there is an urgent need to document that teratology counseling, in addition to improving the quality of life of women and families, also leads to cost saving. The objective of the present study was to calculate the cost effectiveness of the Motherisk Program, a large teratology information and counseling service at The Hospital for Sick Children and the University of Toronto. We analyzed data from the Motherisk Program on its 2012 activities in two domains: 1) Calculation of cost-saving in preventing unjustified pregnancy terminations; and 2) prevention of major birth defects. Cost of pregnancy termination and lifelong cost of specific birth defects were identified from primary literature and prorated for cost of living for the year 2013. Prevention of 255 pregnancy terminations per year led to cost savings of $516,630. The total estimated number of major malformations prevented by Motherisk counseling in 2012 was 8.41 cases at a total estimated cost of $9,032,492. With an estimated minimum annual prevention of 8 major malformations, and numerous unnecessary terminations of otherwise- wanted pregnancies, a cost saving of $10 million can be calculated. In 2013 the operating budget of Motherisk counseling totaled $640,000. Even based on the narrow range of activities for which we calculated cost, this service is highly cost- effective. Because most teratology counseling services are operating in a very similar method to Motherisk, it is fair to assume that these results, although dependent on the size of the service, are generalizable to other countries.

Teratology on the crossroads: historical aspects and modern approaches.

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Ujházy, Eduard; Mach, Mojmír; Navarová, Jana; Dubovický, Michal

2012-01-01

Teratology is the science of congenital developmental disorders (CDDs), overt or latent defects of the organism resulting from the effect of internal and external factors on developmental processes. In this article the significance and position of present-day teratology is discussed in the context of development of this branch of science and related disciplines. The authors present an updated overview of the most important milestones and stages of the development of teratology. Based on the analysis of the historical development of theses and theories that represent a decisive contribution to this field, we present a survey of the fundamental principles of experimental and clinical teratology. The aim of observing these principles is to get insight into developmental relations and to understand mechanisms of action on the level of cell populations (elementary morphogenetic processes), tissues and organs. It is important to realize that any negative intervention into the normal course of these processes, either on genetic or non-genetic basis, inevitably leads to a sequence of subsequent changes resulting in the development of congenital developmental disorders. Despite modern approaches of molecular biology and genetics, along with top diagnostic techniques, we are still not able to identify the actual cause in more than 50% of all congenital defects. One-half of the unidentified cases are referred to as "multifactorial", a term that is rather ambiguous. It either means that some of the basic principles of teratogenesis still escape our attention, or the interpretation of some of the well known principles might be misleading. A third possibility is rather pessimistic. The development of the individual is so sophisticated and dependent on a delicate network of a multitude of factors mutually affecting each other that it is extremely prone to give rise to a plethora of spontaneous errors which are unpredictable and impossible to prevent. Nevertheless, the long and

[Wilson's principles--a base of modern teratology].

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Burdan, Franciszek; Bełzek, Artur; Szumiło, Justyna; Dudka, Jarosław; Korobowicz, Agnieszka; Tokarska, Edyta; Klepacz, Lidia; Bełzek, Marta; Klepacz, Robert

2006-03-01

Wilson's principles were formulated after thalidomide tragedy. They become a fundamental for teratological studies with drugs and other factors that may disturb fetal development. It is postulated that susceptibility to teratogen depends on the genotype and developmental stage of the conceptus. Teratogenic agents act in specific manner on developing cells and tissues. The exposition depends on the agent's nature and availability. Manifestations of deviant development depends on the dosage and exposure frequency. In case of abnormal development the final manifestations include death of embryo or fetus, malformation, growth retardation and functional disorder.

The effectiveness of Teratology Information Services (TIS).

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Hancock, Rebecca L; Koren, Gideon; Einarson, Adrienne; Ungar, Wendy J

2007-02-01

Women and their health care providers have few reliable sources of information regarding the safety of exposures in pregnancy and lactation. Evidence-based information on these topics is provided by Teratology Information Services (TIS). Access to TIS, however, is limited in many regions, and many services have difficulty maintaining ongoing funding. The objective of this review is to highlight published reports of the effectiveness of TIS in improving maternal and neonatal health. A search of the Pub Med and Econ Lit databases was performed with no date restriction, using the search terms teratology, information, counseling, pregnancy, effectiveness, birth defects. Information disseminated from TIS has been shown to prevent congenital malformations, unnecessary pregnancy terminations, and occupational risks. TIS support optimal nutritional supplementation in pregnancy and optimal drug therapy in pregnancy and breast-feeding. In addition, they correct misperceptions of risk and facilitate knowledge transfer and translation. TIS have the potential to provide health care cost savings. TIS are vital services in supporting optimal maternal and neonatal health. A formal economic evaluation of TIS is required in order to inform resource allocation decision-making and continued funding of these services.

Development, anatomy, and genetic control of some teratological phenotypes of Ranunculaceae flowers

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Florian Jabbour

2016-04-01

Full Text Available Teratological organisms originate from developmental anomalies, and exhibit structures and a body organization that deviate from the species standard. These monsters give essential clues about the formation and evolutionary significance of the wild-type groundplan. We focus on flower terata, which can be affected in their sterile and/or fertile organs, with special emphasis on the Ranunculaceae. The diversity of perianth shapes and organizations in flowers of this family is huge, and is even increased when anomalies occur during organo- and/or morphogenesis. To begin with, we synthesize the observations and research conducted on the Ranunculacean floral terata, following the most recent phylogenetic framework published in 2016 by our team. Then, we report results regarding the morphology of developing meristems, the anatomy of buds, and the genetic control of selected teratological phenotypes of Ranunculaceae flowers. We focus on species and horticultural varieties belonging to the genera Aquilegia, Delphinium, and Nigella. Wildtype flowers of these species are actinomorphic (Aquilegia, Nigella or zygomorphic (Delphinium, spurred (Aquilegia, Delphinium or with pocket-like petals (Nigella. Last, we discuss the evolutionary potential of such teratological phenotypes when they occur in the wild.

Introduction: biomarkers in neurodevelopment toxicology

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Needleman, H.L.

1987-10-01

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.

[From teratology to mythology: ancient legends].

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Stahl, A; Tourame, P

2010-12-01

The mythology of the Greeks and Romans is full of monsters of fiction: giants, cyclops, centaurs, hydras, Gorgons… The accounts of travelers, reproduced in the Natural History of Pline l'Ancien reported the existence, in distant countries, of men with a dog's head (baboons), of men with a single tall foot (sciapode), beings whose face is embedded in the chest (or acephala blemmyes), to which must be added a wide variety of men with no mouth, no nose, or equipped with giant ears or feet turned backwards, as well as hermaphrodites. Teratology reports on monstrous births, which have constituted the factual basis from which the imagination conceived adults whose morphology corresponds to the monsters of legend. Newborns sirenomelia were behind the legend of sciapode and sirens. Cyclopia have inspired the legend of the cyclops. Anencephaly probably explains the description of headless or blemmyes. The genesis of the legend of baboons may have multiple origins: firstly the existence of people suffering from congenital hypertrichosis, on the other hand, the influence of Egyptian mythology where the god Anubis has a dog's head. The acardiac fetus may explain some monstrous forms, features the work of Hieronymus Bosch. The significance of the monsters of legend, their genesis, their persistence through the ages is complex. By approaching teratology, we added a new field of exploration of real monsters of antiquity and Middle Ages. Copyright © 2010. Published by Elsevier SAS.

Toxicology and teratology of the active ingredients of professional therapy MuscleCare products during pregnancy and lactation: a systematic review.

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Alsaad, Abdulaziz M S; Fox, Colleen; Koren, Gideon

2015-03-05

The rates of muscle aches, sprains, and inflammation are significantly increased during pregnancy. However, women are afraid to use systemic analgesics due to perceptions of fetal risks. Thus, topical products are important alternatives to consider for those women. Of interest, Professional Therapy MuscleCare (PTMC) has shown to be effective in alleviating the myofascial pain as reported in a randomized, placebo-controlled double-blinded comparative clinical study of five topical analgesics. However, to date, there is no complete review or long-term safety studies on the safety of these products during pregnancy and lactation. Thus, the aim of this article was to review toxicological, developmental, and reproductive effects associated with the use of PTMC products. We performed a systematic review on safety of PTMC from all toxicological articles investigating the effects of PTMC's ingredients. This search was conducted through medical and toxicological databases including, Web of Science, EMBASE, Medline, and Micromedix. Both reported and theoretical adverse effects were extensively reviewed. Of the 1500 publications reviewed, 100 papers were retrieved and included in the review. Although some ingredients in PTMC products might cause adverse reproductive effects at high systemic doses, these doses are hundreds to thousands fold greater than those systemically available from topical use at the recommended maximum dose (i.e. 10 g/day). This study provides evidence that, when used as indicated, PTMC is apparently safe for pregnant women and their unborn babies as well as for breastfed infants.

The Teratology Society 2007 strategic planning session: a desire to inspire.

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2008-05-01

On April 18-20, 2007, the Teratology Society held its third strategic planning session (SPS) in San Diego, CA. The purpose of this session was to build on the successful work generated by the previous strategic plans [Nashville, TN 2002 and Cincinnati, OH 1997] and importantly, to provide a path forward to inspire the Society, create deeper connections with members that speak to their individual passion for the science of teratology and to increase the Society's visibility within the larger scientific community. The following summary report provides an overview of the session's pre-work, objective, and discussions. A total of 24 attendees were present at the session. The group included representation from Council, various committees and different members constituencies. This plan and the activities subsequent to the session will provide a path forward for our Society for the next five years.

The teratology society 2012-2017 strategic plan: pushing the boundaries.

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Curran, Christine Perdan; Lau, Christopher; Schellpfeffer, Michael A; Stodgell, Christopher J; Carney, Edward W

2013-01-01

The Teratology Society held its fourth strategic planning session in Albuquerque, NM, April 10-12, 2012, and launched the 2012-2017 Strategic Plan in conjunction with the 2012 annual meeting in Baltimore, MD. Building on the energy of the successful implementation of prior strategic plans (San Diego, 2007; Nashville,TN 2002; Cincinnati, OH 1998), session participants worked to identify barriers to success as a scientific society, as well as impending challenges and opportunities to which the Society needs to respond. The following report provides an overview of the Strategic Planning process, objectives, activities, and conclusions. A total of 23 members were present at the session, and the group included representation from Council, various committees, and different member constituencies. This plan, Pushing the Boundaries, and its three strategic intents: Broaden Our Identity, Expand Our Membership, and Increase Our Influence, will drive the direction of the Teratology Society for the next five years. Copyright © 2013 Wiley Periodicals, Inc.

Drug safety in pregnancy: utopia or achievable prospect? Risk information, risk research and advocacy in Teratology Information Services.

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Schaefer, Christof

2011-03-01

Even though from preclinical testing to drug risk labeling, the situation with drugs in pregnancy has improved substantially since the thalidomide scandal, there is still an increasing need to provide healthcare professionals and patients with updated individualized risk information for clinical decision making. For the majority of drugs, clinical experience is still insufficient with respect to their safety in pregnancy. There is often uncertainty in how to interpret the available scientific data. Based on 20 years of experience with Teratology Information Services (TIS) cooperating in the European Network of Teratology Information Services (ENTIS) methods of risk interpretation, follow-up of exposed pregnancies through the consultation process and their evaluation is discussed. Vitamin K antagonists, isotretinoin and angiotensin (AT) II-receptor-antagonists are presented as examples of misinterpretation of drug risks and subjects of research based on observational clinical data recorded in TIS. As many TIS are poorly funded, advocacy is necessary by establishing contacts with decision makers in health politics and administration, informing them of the high return in terms of health outcomes and cost savings provided by TIS as reference institutions in clinical teratology. © 2011 The Author. Congenital Anomalies © 2011 Japanese Teratology Society.

Understanding the cone scale in Cupressaceae: insights from seed-cone teratology in Glyptostrobus pensilis.

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Dörken, Veit Martin; Rudall, Paula J

2018-01-01

Both wild-type and teratological seed cones are described in the monoecious conifer Glyptostrobus pensilis and compared with those of other Cupressaceae sensu lato and other conifers. Some Cupressaceae apparently possess a proliferation of axillary structures in their cone scales. In our interpretation, in Glyptostrobus each bract of both typical and atypical seed cones bears two descending accessory shoots, interpreted here as seed scales (ovuliferous scales). The primary seed scale is fertile and forms the ovules, the second is sterile and forms characteristic tooth-like structures. The bract and the two axillary seed scales are each supplied with a single distinct vascular bundle that enters the cone axis as a separate strand; this vasculature also characterises the descending accessory short shoots in the vegetative parts of the crown. In wild-type seed cones, the fertile seed scale is reduced to its ovules, and the ovules are always axillary. In contrast, the ovules of some of the teratological seed cones examined were located at the centre of the cone scale. An additional tissue found on the upper surface of the sterile lower seed scale is here interpreted as the axis of the fertile seed scale. Thus, the central position of the ovules can be explained by recaulescent fusion of the upper fertile and lower sterile seed scales. In several teratological cone scales, the ovules were enveloped by an additional sterile tissue that is uniseriate and represents an epidermal outgrowth of the fertile seed scale. Close to the ovules, the epidermis was detached from lower tissue and surrounded the ovule completely, except at the micropyle. These teratological features are potentially significant in understanding seed-cone homologies among extant conifers.

Understanding the cone scale in Cupressaceae: insights from seed-cone teratology in Glyptostrobus pensilis

Directory of Open Access Journals (Sweden)

Veit Martin Dörken

2018-06-01

Full Text Available Both wild-type and teratological seed cones are described in the monoecious conifer Glyptostrobus pensilis and compared with those of other Cupressaceae sensu lato and other conifers. Some Cupressaceae apparently possess a proliferation of axillary structures in their cone scales. In our interpretation, in Glyptostrobus each bract of both typical and atypical seed cones bears two descending accessory shoots, interpreted here as seed scales (ovuliferous scales. The primary seed scale is fertile and forms the ovules, the second is sterile and forms characteristic tooth-like structures. The bract and the two axillary seed scales are each supplied with a single distinct vascular bundle that enters the cone axis as a separate strand; this vasculature also characterises the descending accessory short shoots in the vegetative parts of the crown. In wild-type seed cones, the fertile seed scale is reduced to its ovules, and the ovules are always axillary. In contrast, the ovules of some of the teratological seed cones examined were located at the centre of the cone scale. An additional tissue found on the upper surface of the sterile lower seed scale is here interpreted as the axis of the fertile seed scale. Thus, the central position of the ovules can be explained by recaulescent fusion of the upper fertile and lower sterile seed scales. In several teratological cone scales, the ovules were enveloped by an additional sterile tissue that is uniseriate and represents an epidermal outgrowth of the fertile seed scale. Close to the ovules, the epidermis was detached from lower tissue and surrounded the ovule completely, except at the micropyle. These teratological features are potentially significant in understanding seed-cone homologies among extant conifers.

Acute, reproductive toxicity and two-generation teratology studies of a standardized quassinoid-rich extract of Eurycoma longifolia Jack in Sprague-Dawley rats.

Science.gov (United States)

Low, Bin-Seng; Das, Prashanta Kumar; Chan, Kit-Lam

2014-07-01

The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies. Copyright © 2013 John Wiley & Sons, Ltd.

Applying Evolutionary Genetics to Developmental Toxicology and Risk Assessment

Science.gov (United States)

Leung, Maxwell C. K.; Procter, Andrew C.; Goldstone, Jared V.; Foox, Jonathan; DeSalle, Robert; Mattingly, Carolyn J.; Siddall, Mark E.; Timme-Laragy, Alicia R.

2018-01-01

Evolutionary thinking continues to challenge our views on health and disease. Yet, there is a communication gap between evolutionary biologists and toxicologists in recognizing the connections among developmental pathways, high-throughput screening, and birth defects in humans. To increase our capability in identifying potential developmental toxicants in humans, we propose to apply evolutionary genetics to improve the experimental design and data interpretation with various in vitro and whole-organism models. We review five molecular systems of stress response and update 18 consensual cell-cell signaling pathways that are the hallmark for early development, organogenesis, and differentiation; and revisit the principles of teratology in light of recent advances in high-throughput screening, big data techniques, and systems toxicology. Multiscale systems modeling plays an integral role in the evolutionary approach to cross-species extrapolation. Phylogenetic analysis and comparative bioinformatics are both valuable tools in identifying and validating the molecular initiating events that account for adverse developmental outcomes in humans. The discordance of susceptibility between test species and humans (ontogeny) reflects their differences in evolutionary history (phylogeny). This synthesis not only can lead to novel applications in developmental toxicity and risk assessment, but also can pave the way for applying an evo-devo perspective to the study of developmental origins of health and disease. PMID:28267574

Czech Teratology Information Service: comparison of treatments by psychotropic and antiepileptic drugs.

Science.gov (United States)

Manáková, Eva; Hubicková-Heringová, Lucie; Jelínek, Richard

2006-12-01

Care, treatment and follow-up in psychiatric and epileptic pregnant women were compared with women inquiring Czech Teratology Information Service (CZTIS) due to other exposure to drugs during pregnancy. Data were collected by CZTIS, member of European Network of Teratology Information Services from 1996. Exposed groups were compared with pregnant women exposed to drugs which were not classified as major teratogens or hyperthermia. Groups do not vary in age, reproductive history and other parameters. We observed higher frequency of miscarriage and voluntary termination of pregnancy in the group of psychiatric patients. The number of malformation in prospective follow-up cases was lower than in control group. Chronic diseases as epilepsy or psychiatric disorders have to be treated during pregnancy. Women should obtain accurate information about possible risk before pregnancy. Co-operation is needed in these cases. Physicians should keep in mind that appropriate information is to be given to the patient according to her disease, education and comprehension of the problem. If there is any doubt they should organize help for their patients.

An updated history of the Teratology Society.

Science.gov (United States)

Shepard, Thomas H; Barr, Mason; Brent, Robert L; Hendrickx, Andrew; Kochhar, Devendra; Oakley, Godfrey; Scott, William J; Rogers, John M

2010-05-01

The 49-year history of the Teratology Society is reviewed. An abbreviated history is outlined in table form, with listings of the Warkany Lectures, the Continuing Education Courses, and officers of the society. The original article was updated to include the years 2000 to 2010. A year-by-year description of the events is given, including the scientific and social content of the annual meetings and changes in the business of the society, in many cases using comments from the past presidents. The valuable and unique diversity of the members is discussed and illustrated, presenting the disciplines and main research areas of the presidents. The number of submitted abstracts and the various categories are tabulated, averaging the number and type over successive periods. A significant increase in the number of abstracts dealing with epidemiology and developmental biology is evident. The society's development is compared to that of a human, and the question was asked by Shephard et al. (2000): Have we reached the maturational stage of old age or senescence, or is the society still maturing gracefully? This question needs further discussion by all the members. By 2010, many positive changes are happening to revitalize the society. During the past 50 years, we have developed the scientific basis to prevent birth defects caused by rubella, alcoholism, and folate deficiency, as well as other prenatal exposures. We are now taking advantage of advances in many fields to begin shaping the Teratology Society of the 21st century. We must now engage in political battles to obtain the resources needed to conduct further research and to implement prevention programs, as well as to provide care and rehabilitation for persons with birth defects. 2010 Wiley-Liss, Inc.

Toxicology elements

International Nuclear Information System (INIS)

Viala, A.

1998-01-01

This work studies the different aspects of the modern toxicology: toxico-kinetic, biological, medico legal, food, professional, pharmaceuticals, environmental, social and regulatory. It is divided in three parts that consider the principle problems of general toxicology and analytical toxicology. (N.C.)

TERATOLOGY SOCIETY 1998 PUBLIC AFFAIRS COMMITTEE SYMPOSIUM: THE NEW THALIDOMIDE ERA: DEALING WITH THE RISKS

Science.gov (United States)

The Teratology Society Public Affairs Committee Symposium was held on June 21, 1998, during the Society's annual meeting in San Diego, California. The symposium was organized and chaired by Dr. Carole Kimmel. The sysmposium was designed to consider the medical, social, and ethi...

Application of Model Animals in the Study of Drug Toxicology

Science.gov (United States)

Song, Yagang; Miao, Mingsan

2018-01-01

Drug safety is a key factor in drug research and development, Drug toxicology test is the main method to evaluate the safety of drugs, The body condition of an animal has important implications for the results of the study, Previous toxicological studies of drugs were carried out in normal animals in the past, There is a great deviation from the clinical practice.The purpose of this study is to investigate the necessity of model animals as a substitute for normal animals for toxicological studies, It is expected to provide exact guidance for future drug safety evaluation.

Assessing the scientific research productivity of a leading toxicology journal: A case study of Human & Experimental Toxicology from 2003 to 2012.

Science.gov (United States)

Zyoud, Sa'ed H; Al-Jabi, Samah W; Sweileh, Waleed M; Awang, Rahmat

2014-01-01

Bibliometric studies are increasingly being used for research assessments. Bibliometric indicators involve the application of statistical methods to scientific publications to obtain the bibliographics for each journal. The main objective of this study was to conduct a bibliometric evaluation of Human & Experimental Toxicology retrieved from the Scopus database. This study obtained data from Scopus published from 1 January 2003 till 31 December 2012. The keywords entered in Scopus to accomplish the objective of this study were 'Human', 'Experimental' and 'Toxicology' as 'Source Title'. Research productivity was evaluated based on a methodology developed and used in other bibliometric studies by analysing (a) total and trends in Human & Experimental Toxicology contributions in research between 2003 and 2012; (b) Human & Experimental Toxicology authorship patterns and productivity; (c) collaboration patterns; and (d) the citations received by the publications. There were 1229 research articles published in Human & Experimental Toxicology. Of the articles included, 947 (77.1%) were original articles and 104 (8.5%) were review articles. The Hirsch-index of the retrieved documents was 35. The largest number of publications in Human & Experimental Toxicology was from the United States (19.6%), followed by India (12.8%) and Turkey (10.9%). The total number of citations was 9119, with a median (interquartile range) of 3 (1-9) in 6797 documents. The highest median (interquartile range) number of citations was 8 (2.7-12.7) for France, followed by 7.5 (2-22.5) for Iran and 6 (3-13.5) for the United Kingdom. The country most often citing articles that were published in Human & Experimental Toxicology was the United States, which made citations in 1508 documents, followed by India with citations in 792 documents. The documents in Human & Experimental Toxicology focus principally on original data, with very few review articles. Review articles tend to have higher citation rates

History and highlights of the teratological collection in the Museum Anatomicum of Leiden University, The Netherlands

NARCIS (Netherlands)

Boer, Lucas L.; Boek, Peter L. J.; van Dam, Andries J.; Oostra, Roelof-Jan

2018-01-01

The anatomical collection of the Anatomical Museum of Leiden University Medical Center (historically referred to as Museum Anatomicum Academiae Lugduno-Batavae) houses and maintains more than 13,000 unique anatomical, pathological and zoological specimens, and include the oldest teratological

Reproductive studies with the anti-inflammatory agent, piroxicam: modification of classical protocols.

Science.gov (United States)

Perraud, J; Stadler, J; Kessedjian, M J; Monro, A M

1984-02-14

Reproductive toxicology studies were conducted in rabbits and rats given piroxicam, a non-steroidal anti-inflammatory agent (NSAI), orally at 2, 5 and 10 mg/kg/day. In teratology studies there was neither drug-related embryotoxicity nor teratogenicity. As piroxicam, like other NSAI, affects parturition in rats and leads to a progressive toxicity in lactating females, standard protocols were modified: dams of the female fertility study were treated from 2 weeks prior to mating until day 6 of gestation and females of the post-natal toxicity study were treated from parturition until day 12 of lactation. No other adverse effects on reproduction, fertility and postnatal development were observed.

Mammalian Genetics and Teratology Section

International Nuclear Information System (INIS)

Anon.

1980-01-01

The work of the Mammalian Genetics and Teratology Section includes research in mutagenesis, basic genetics, reproductive biology, and teratogenesis involving basic studies, method development, including exploration of the biological material, and testing. The basic studies make good use of the genetic material accumulated in mutagenesis experiments of various kinds, or of the findings of mutagenesis experiments themselves. In the latter category is the finding of a repair system in the fertilized egg. The genetics of repair competency or deficiency are now under study. A linear relationship between gene dosage and level of expression of an enzyme has been demonstrated. Opportunities for the study of gene action are provided by a number of X-autosome translocations which continue to be discovered in the course of mutagenesis experiments. In these rearrangements, X-chromosome inactivation extends to neighboring autosomal loci. Considerable progress has been made in developing the skeletal mutation system, which provides information on dominants that is highly useful for risk assessment. A sensitive-indicator test is now under development which will make the screening for skeletal mutations much faster and easier. Method development has also progressed on the in vivo somatic-mutation test now being widely used as an in vivo screen for mutagens. Another method developed here is the numerical sex-chromosome anomaly (NSA) test for nondisjunction. The NSA method is being used to explore the effects of female age on chromosome loss and nondisjunction. A model for estimating the misclassification error was experimentally established for the heritable translocation test. A rapid, easy, and sensitive in vivo screening test for teratogenesis was developed. An in vitro teratogenic prescreen being developed makes use of teratocarcinoma-derived cell lines

Assessing the scientific research productivity of a leading toxicology journal: A case study of Human & Experimental Toxicology from 2003 to 2012

Science.gov (United States)

Al-Jabi, Samah W; Sweileh, Waleed M; Awang, Rahmat

2014-01-01

Background: Bibliometric studies are increasingly being used for research assessments. Bibliometric indicators involve the application of statistical methods to scientific publications to obtain the bibliographics for each journal. The main objective of this study was to conduct a bibliometric evaluation of Human & Experimental Toxicology retrieved from the Scopus database. Methods: This study obtained data from Scopus published from 1 January 2003 till 31 December 2012. The keywords entered in Scopus to accomplish the objective of this study were ‘Human’, ‘Experimental’ and ‘Toxicology’ as ‘Source Title’. Research productivity was evaluated based on a methodology developed and used in other bibliometric studies by analysing (a) total and trends in Human & Experimental Toxicology contributions in research between 2003 and 2012; (b) Human & Experimental Toxicology authorship patterns and productivity; (c) collaboration patterns; and (d) the citations received by the publications. Results: There were 1229 research articles published in Human & Experimental Toxicology. Of the articles included, 947 (77.1%) were original articles and 104 (8.5%) were review articles. The Hirsch-index of the retrieved documents was 35. The largest number of publications in Human & Experimental Toxicology was from the United States (19.6%), followed by India (12.8%) and Turkey (10.9%). The total number of citations was 9119, with a median (interquartile range) of 3 (1–9) in 6797 documents. The highest median (interquartile range) number of citations was 8 (2.7–12.7) for France, followed by 7.5 (2–22.5) for Iran and 6 (3–13.5) for the United Kingdom. The country most often citing articles that were published in Human & Experimental Toxicology was the United States, which made citations in 1508 documents, followed by India with citations in 792 documents. Conclusion: The documents in Human & Experimental Toxicology focus principally on original data, with very few

Metabonomics and toxicology.

Science.gov (United States)

Zhao, Liang; Hartung, Thomas

2015-01-01

Being an emerging field of "omics" research, metabonomics has been increasingly used in toxicological studies mostly because this technology has the ability to provide more detailed information to elucidate mechanism of toxicity. As an interdisciplinary field of science, metabonomics combines analytical chemistry, bioinformatics, statistics, and biochemistry. When applied to toxicology, metabonomics also includes aspects of patho-biochemistry, systems biology, and molecular diagnostics. During a toxicological study, the metabolic changes over time and dose after chemical treatment can be monitored. Therefore, the most important use of this emerging technology is the identification of signatures of toxicity-patterns of metabolic changes predictive of a hazard manifestation. This chapter summarizes the current state of metabonomics technology and its applications in various areas of toxicological studies.

Recommendations for harmonization of data collection and analysis of developmental neurotoxicity endpoints in regulatory guideline studies: Proceedings of workshops presented at Society of Toxicology and joint Teratology Society and Neurobehavioral Teratology Society meetings.

Science.gov (United States)

Li, Abby A; Sheets, Larry P; Raffaele, Kathleen; Moser, Virginia; Hofstra, Angela; Hoberman, Alan; Makris, Susan L; Garman, Robert; Bolon, Brad; Kaufmann, Wolfgang; Auer, Roland; Lau, Edmund; Vidmar, Thomas; Bowers, Wayne J

2017-09-01

The potential for developmental neurotoxicity (DNT) of environmental chemicals may be evaluated using specific test guidelines from the US Environmental Protection Agency or the Organisation for Economic Cooperation and Development (OECD). These guidelines generate neurobehavioral, neuropathological, and morphometric data that are evaluated by regulatory agencies globally. Data from these DNT guideline studies, or the more recent OECD extended one-generation reproductive toxicity guideline, play a pivotal role in children's health risk assessment in different world areas. Data from the same study may be interpreted differently by regulatory authorities in different countries resulting in inconsistent evaluations that may lead to inconsistencies in risk assessment decisions internationally, resulting in regional differences in public health protection or in commercial trade barriers. These issues of data interpretation and reporting are also relevant to juvenile and pre-postnatal studies conducted more routinely for pharmaceuticals and veterinary medicines. There is a need for development of recommendations geared toward the operational needs of the regulatory scientific reviewers who apply these studies in risk assessments, as well as the scientists who generate DNT data sets. The workshops summarized here draw upon the experience of the authors representing government, industry, contract research organizations, and academia to discuss the scientific issues that have emerged from diverse regulatory evaluations. Although various regulatory bodies have different risk management decisions and labeling requirements that are difficult to harmonize, the workshops provided an opportunity to work toward more harmonized scientific approaches for evaluating DNT data within the context of different regulatory frameworks. Five speakers and their coauthors with neurotoxicology, neuropathology, and regulatory toxicology expertise discussed issues of variability, data reporting

THE USE OF STEM CELLS FOR TOXICOLOGY STUDIES AND RISK ASSESSMENTS

Science.gov (United States)

In general terms, toxicology studies are used in support of risk assessments of adverse health outcomes as a result of exposures to chemical and physical agents. In particular, toxicological data are used to provide information that aids in the assessment of disease outcomes at e...

Biochemical and toxicological studies of aqueous extract of ...

African Journals Online (AJOL)

Biochemical and toxicological studies of aqueous extract of Syzigium ... tract diseases and also used as food spices), on some biochemical indices, such as ... liver functions and blood parameters were studied in adult albino rats of both sexes.

Pre implanted mouse embryos as model for uranium toxicology studies

International Nuclear Information System (INIS)

Kundt, Miriam S.

2001-01-01

Full text: The search of 'in vitro' toxicology model that can predict toxicology effects 'in vivo' is a permanent challenge. A toxicology experimental model must to fill to certain requirements: to have a predictive character, an appropriate control to facilitate the interpretation of the data among the experimental groups, and to be able to control the independent variables that can interfere or modify the results that we are analyzing. The preimplantation embryos posses many advantages in this respect: they are a simple model that begins with the development of only one cell. The 'in vitro' model reproduces successfully the 'in vivo' situation. Due to the similarity that exists among the embryos of mammals during this period the model is practically valid for other species. The embryo is itself a stem cell, the toxicology effects are early observed in his clonal development and the physical-chemical parameters are easily controllable. The purpose of the exhibition is to explain the properties of the pre implanted embryo model for toxicology studies of uranium and to show our experimental results. The cultivation 'in vitro' of mouse embryos with uranylo nitrate demonstrated that the uranium causes from the 13 μgU/ml delay of development, decrease the number of cells per embryo and hipoploidy in the embryonic blastomere. (author)

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.

2011-01-01

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

[The Teratology Information Service: medicines during pregnancy and lactation].

Science.gov (United States)

de Vries, Loes C; de Swart, Irene W; van Puijenbroek, Eugène P

2016-01-01

Many women use medication during pregnancy. Both the healthcare professional and the pregnant woman often have many questions about the possible adverse effects of the medication that are not always answered in the product information. The Teratology Information Service (TIS), a part of the Netherlands Pharmacovigilance Centre Lareb, is a centre of expertise in the field of the safety of medication use and other external influences during spermatogenesis, pregnancy and lactation. The TIS collects, interprets, and disseminates information that can contribute to patient care. Healthcare professionals can contact the TIS for information and individual risk assessments. In this article we discuss the background and positioning of the TIS, the characteristics of telephone consultations, the collection of data and the considerations that are important for the use of medication during pregnancy and lactation.

The application of capillary microsampling in GLP toxicology studies.

Science.gov (United States)

Verhaeghe, Tom; Dillen, Lieve; Stieltjes, Hans; Zwart, Loeckie de; Feyen, Bianca; Diels, Luc; Vroman, Ann; Timmerman, Philip

2017-04-01

Capillary microsampling (CMS) to collect microplasma volumes is gradually replacing traditional, larger volume sampling from rats in GLP toxicology studies. About 32 µl of blood is collected with a capillary, processed to plasma and stored in a 10- or 4-µl capillary which is washed out further downstream in the laboratory. CMS has been standardized with respect to materials, assay validation experiments and application for sample analysis. The implementation of CMS has resulted in blood volume reductions in the rat from 300 to 32 µl per time point and the elimination of toxicokinetic satellite groups in the majority of the rat GLP toxicology studies. The technique has been successfully applied in 26 GLP studies for 12 different projects thus far.

Green toxicology.

Science.gov (United States)

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

2014-01-01

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

Forensic toxicology.

Science.gov (United States)

Davis, Gregory G

2012-01-01

Toxicologic analysis is an integral part of death investigation, and the use or abuse of an unsuspected substance belongs in the differential diagnosis of patients who have a sudden, unexpected change in their condition. History and physical findings may alter suspicion that intoxication played a role in a patient's decline or death, but suspicions cannot be confirmed and is performed, analysis unless toxicologic no toxicologic analysis is possible unless someone collects the proper specimens necessary for analysis. In a hospital autopsy the only specimens that can rightfully be collected are those within the restrictions stated in the autopsy permit. Autopsies performed by the medical examiner do not have these restrictions. Sometimes the importance of toxicologic testing in a case is not evident until days or weeks after the change in the patient's status, thus retaining the appropriate specimens until investigation of that case has ended is important. Proper interpretation of toxicologic findings requires integrating the clinical setting and findings with the toxicologic results in a way that makes medical sense. If called upon to testify concerning findings, answer the questions truthfully, politely, and in a way that is understandable to someone who has no special training in toxicology.

Animal-free toxicology

DEFF Research Database (Denmark)

Knudsen, Lisbeth E

2013-01-01

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....

Cornerstones of Toxicology.

Science.gov (United States)

Hayes, A Wallace; Dixon, Darlene

2017-01-01

The 35th Annual Society of Toxicologic Pathology Symposium, held in June 2016 in San Diego, California, focused on "The Basis and Relevance of Variation in Toxicologic Responses." In order to review the basic tenants of toxicology, a "broad brush" interactive talk that gave an overview of the Cornerstones of Toxicology was presented. The presentation focused on the historical milestones and perspectives of toxicology and through many scientific graphs, data, and real-life examples covered the three basic principles of toxicology that can be summarized, as dose matters (as does timing), people differ, and things change (related to metabolism and biotransformation).

Mass Spectrometry Applications for Toxicology.

Science.gov (United States)

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

2016-12-01

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.

Mass Spectrometry Applications for Toxicology

Science.gov (United States)

Mbughuni, Michael M.; Jannetto, Paul J.

2016-01-01

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. PMID:28149262

The Toxicology Education Summit: building the future of toxicology through education.

Science.gov (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

2012-06-01

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.

A practice analysis of toxicology.

Science.gov (United States)

Wood, Carol S; Weis, Christopher P; Caro, Carla M; Roe, Amy

2016-12-01

In 2015, the American Board of Toxicology (ABT), with collaboration from the Society of Toxicology (SOT), in consultation with Professional Examination Service, performed a practice analysis study of the knowledge required for general toxicology. The purpose of this study is to help assure that the examination and requirements for attainment of Diplomate status are relevant to modern toxicology and based upon an empirical foundation of knowledge. A profile of the domains and tasks used in toxicology practice was developed by subject-matter experts representing a broad range of experiences and perspectives. An on-line survey of toxicologists, including Diplomates of the ABT and SOT members, confirmed the delineation. Results of the study can be used to improve understanding of toxicology practice, to better serve all toxicologists, and to present the role of toxicologists to those outside the profession. Survey results may also be used by the ABT Board of Directors to develop test specifications for the certifying examination and will be useful for evaluating and updating the content of professional preparation, development, and continuing education programs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Inhalation developmental toxicology studies: Teratology study of isoprene in mice and rats: Final report

Energy Technology Data Exchange (ETDEWEB)

Mast, T.J.; Evanoff, J.J.; Stoney, K.H.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

1989-01-01

Isoprene, a reactive, branched diene, is used in large quantities in the manufacture of polyisoprene and as a copolymer in the synthesis of butyl rubber. The potential for isoprene to cause developmental toxicity was assessed in rodents, by exposing four groups each of Sprague-Dawley rats and Swiss (CD-1) mice to 0, 280, 1400, or 7000 ppM isoprene vapors, 6 h/day, 7 day/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.30 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 31 refs., 6 figs., 19 tabs.

Inhalation developmental toxicology studies: Teratology study of acetone in mice and rats: Final report

Energy Technology Data Exchange (ETDEWEB)

Mast, T.J.; Evanoff, J.J.; Rommereim, R.L.; Stoney, K.H.; Weigel, R.J.; Westerberg, R.B.

1988-11-01

Acetone, an aliphatic ketone, is a ubiquitous industrial solvent and chemical intermediate; consequently, the opportunity for human exposure is high. The potential for acetone to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 440, 2200, or 11000 ppm, and in Swiss (CD-1) mice exposed to 0, 440, 2200, and 6600 ppm acetone vapors, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and approx.32 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 46 refs., 6 figs., 27 tabs.

Inhalation developmental toxicology studies: Teratology study of methyl ethyl ketone in mice: Final report

Energy Technology Data Exchange (ETDEWEB)

Mast, T.J.; Dill, J.A.; Evanoff, J.J.; Rommereim, R.L.; Weigel, R.J.; Westerberg, R.B.

1989-02-01

Methyl ethyl ketone (MEK) is a widely used industrial solvent which results in considerable human exposure. In order to assess the potential for MEK to cause developmental toxicity in rodents, four groups of Swiss (CD-1) mice were exposed to 0, 400, 1000 or 3000 ppM MEK vapors, 7 h/day, 7 dy/wk. Ten virgin females and approx.30 plug-positive females per group were exposed concurrently for 10 consecutive days (6--15 dg for mated mice). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on 18 dg. Uterine implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Exposure of pregnant mice to these concentrations of MEK did not result in apparent maternal toxicity, although there was a slight, treatment-correlated increase in liver to body weight ratios which was significant for the 3000-ppM group. Mild developmental toxicity was evident at 3000-ppM as a reduction in mean fetal body weight. This reduction was statistically significant for the males only, although the relative decrease in mean fetal body weight was the same for both sexes. 17 refs., 4 figs., 10 tabs.

Inhalation developmental toxicology studies: Teratology study of methyl ethyl ketone in mice: Final report

International Nuclear Information System (INIS)

Mast, T.J.; Dill, J.A.; Evanoff, J.J.; Rommereim, R.L.; Weigel, R.J.; Westerberg, R.B.

1989-02-01

Methyl ethyl ketone (MEK) is a widely used industrial solvent which results in considerable human exposure. In order to assess the potential for MEK to cause developmental toxicity in rodents, four groups of Swiss (CD-1) mice were exposed to 0, 400, 1000 or 3000 ppM MEK vapors, 7 h/day, 7 dy/wk. Ten virgin females and ∼30 plug-positive females per group were exposed concurrently for 10 consecutive days (6--15 dg for mated mice). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on 18 dg. Uterine implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Exposure of pregnant mice to these concentrations of MEK did not result in apparent maternal toxicity, although there was a slight, treatment-correlated increase in liver to body weight ratios which was significant for the 3000-ppM group. Mild developmental toxicity was evident at 3000-ppM as a reduction in mean fetal body weight. This reduction was statistically significant for the males only, although the relative decrease in mean fetal body weight was the same for both sexes. 17 refs., 4 figs., 10 tabs

Green Toxicology – Application of predictive toxicology

DEFF Research Database (Denmark)

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

2014-01-01

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...

[POETRYAND TERATOLOGY: LORENZO MASCHERONI'S "INVITO A LESBIA CIDONIA" IN ANATOMICAL PREPARATIONS].

Science.gov (United States)

Carla, Garbarino; Valentina, Cani; Stefano, Maretti; Paolo, Mazzarello

2015-01-01

In 1793 Lorenzo Mascheroni, appointed to the chair of Mathematics at the University of Pavia and well-known poet, wrote "L'invito di Dafni Orobiano a Lesbia Cidonia". In the poem he described the beauty of the University of Pavia and its wonders gathered in the scientific collections of the museums. From the beginning, one of the glass cases of the Museum for the History of the University of Pavia shows some of the preparations described in the Mascheroni's verses. In addition to some fossils, human teratological preparations are also exposed: they recall the verses of the poem dedicated to the description of "monstrous" preparations. However, after a detailed scientifc and historical research, the traditional association of the exposed anatomical preparations with the verses is questioned.

Information resources in toxicology--Italy

International Nuclear Information System (INIS)

Preziosi, Paolo; Dracos, Adriana; Marcello, Ida

2003-01-01

The purpose of the present paper is to provide an overview of current resources in the field of toxicology in Italy. The discussion will begin with a brief history of toxicology in this country, which includes the study of the toxicity of plants and other natural substances, and the birth of industrial and forensic toxicology. We will also provide information on research, education, and hazard control in the field of toxicology. Within this context we will examine the public bodies responsible for surveillance and regulatory activities, state-owned and private structures involved in toxicological research, and the educational programs and research activities of universities. Particular emphasis will be placed on the activities of the National Health Service, which plays an important role in areas such as clinical toxicology, food safety, and animal health, as well as those of national and regional agencies dedicated to the protection of the environment. The presentation will be organized as follows: - A Brief History of Toxicology in Italy; - Professional Societies; - National Health Service; - National Bodies; - Resources for the Environment; - Biomedical Websites; - Recent Publications; - Research Structures; - Graduate and Postgraduate Programs; - Legislation

The Violation of Childhood: A Review of Possible Effects on Development of Toxic Chemical and Nuclear Waste.

Science.gov (United States)

Evans, Roy

Emphasizing that for any known teratogen no safe dosage level exists, this case-illustrated review identifies the bases for current concern about the pollution of the environment, reflects on the promise and complexities of the emerging disciplines of behavioral toxicology and behavioral teratology, and describes existing evidence of teratogenic…

Precision toxicology based on single cell sequencing: an evolving trend in toxicological evaluations and mechanism exploration.

Science.gov (United States)

Zhang, Boyang; Huang, Kunlun; Zhu, Liye; Luo, Yunbo; Xu, Wentao

2017-07-01

In this review, we introduce a new concept, precision toxicology: the mode of action of chemical- or drug-induced toxicity can be sensitively and specifically investigated by isolating a small group of cells or even a single cell with typical phenotype of interest followed by a single cell sequencing-based analysis. Precision toxicology can contribute to the better detection of subtle intracellular changes in response to exogenous substrates, and thus help researchers find solutions to control or relieve the toxicological effects that are serious threats to human health. We give examples for single cell isolation and recommend laser capture microdissection for in vivo studies and flow cytometric sorting for in vitro studies. In addition, we introduce the procedures for single cell sequencing and describe the expected application of these techniques to toxicological evaluations and mechanism exploration, which we believe will become a trend in toxicology.

Behavioral toxicology in the 21st century: challenges and opportunities for behavioral scientists. Summary of a symposium presented at the annual meeting of the neurobehavioral teratology society, June, 2009.

Science.gov (United States)

Bushnell, Philip J; Kavlock, Robert J; Crofton, Kevin M; Weiss, Bernard; Rice, Deborah C

2010-01-01

be difficult to identify based on screening tests in vitro. Finally, D. Rice raised concerns regarding the use of data derived from toxicity screening tests to human health risk assessments. Discussion centered around opportunities and challenges for behavioral toxicologists regarding this impending paradigm shift. Opportunities include: identifying and characterizing toxicity pathways; informing the conditions and limits of extrapolation; addressing issues of susceptibility and variability; providing reality-checks on selected positives and negatives from screens; and performing targeted testing and dose-response assessments of chemicals flagged during screening. Challenges include: predicting behavior using models of complex neurobiological pathways; standardizing study designs and dependent variables to facilitate creation of databases; and managing the cost and efficiency of behavioral assessments. Thus, while progress is being made in approaching the vision of 21st century toxicology, we remain a long way from replacing whole-animal tests; indeed, some animal testing will be essential for the foreseeable future at least. Initial advances will likely provide better prioritization tools so that animal resources are used more efficiently and effectively.

Toxicology of organic-inorganic hybrid molecules: bio-organometallics and its toxicology.

Science.gov (United States)

Fujie, Tomoya; Hara, Takato; Kaji, Toshiyuki

2016-01-01

Bio-organometallics is a research strategy of biology that uses organic-inorganic hybrid molecules. The molecules are expected to exhibit useful bioactivities based on the unique structure formed by interaction between the organic structure and intramolecular metal(s). However, studies on both biology and toxicology of organic-inorganic hybrid molecules have been incompletely performed. There can be two types of toxicological studies of bio-organometallics; one is evaluation of organic-inorganic hybrid molecules and the other is analysis of biological systems from the viewpoint of toxicology using organic-inorganic hybrid molecules. Our recent studies indicate that cytotoxicity of hybrid molecules containing a metal that is nontoxic in inorganic forms can be more toxic than that of hybrid molecules containing a metal that is toxic in inorganic forms when the structure of the ligand is the same. Additionally, it was revealed that organic-inorganic hybrid molecules are useful for analysis of biological systems important for understanding the toxicity of chemical compounds including heavy metals.

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

International Nuclear Information System (INIS)

Kienhuis, Anne S.; Bessems, Jos G.M.; Pennings, Jeroen L.A.; Driessen, Marja; Luijten, Mirjam; Delft, Joost H.M. van

2011-01-01

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 employed toxicogenomic technologies to date have already provided a proof of principle for the value of hepatic systems toxicology in hazard identification. In the present review, acetaminophen is used as a model compound to discuss the application of toxicogenomics in hepatic systems toxicology for its potential role in the risk assessment process, to progress from hazard identification towards hazard characterization. The toxicogenomics-based parallelogram is used to identify current achievements and limitations of acetaminophen toxicogenomic in vivo and in vitro studies for in vitro-to-in vivo and interspecies comparisons, with the ultimate aim to extrapolate animal studies to humans in vivo. This article provides a model for comparison of more species and more in vitro models enhancing the robustness of common toxicogenomic responses and their relevance to human risk assessment. To progress to quantitative dose-response analysis needed for hazard characterization, in hepatic systems toxicology studies, generation of toxicogenomic data of multiple doses/concentrations and time points is required. Newly developed bioinformatics tools for quantitative analysis of toxicogenomic data can aid in the elucidation of dose-responsive effects. The challenge herein is to assess which toxicogenomic responses are relevant for induction of the apical effect and whether perturbations are sufficient for the induction of downstream events, eventually causing toxicity.

Experimental methods in behavioral teratology

Energy Technology Data Exchange (ETDEWEB)

Zbinden, G.

1981-09-01

Efforts are made to develop toxicological techniques with which new behavioral teratogens can be recognized. The review describes the most important experimental methods which are presently explored, and which are based on a rich body of knowledge accumulated by experimental psychologists. Most of the tests were developed with small animals, mostly with rats. They range from the rather straightforward determination of various reflexes to complex behavioral situations involving mechanical devices, operant conditioning techniques and procedures evaluating social behavior. In applying these methods in routine toxicology, it is important to remember, that many behavioral effects determined in newborn and adult animals are subtle. Moreover, they are influenced by a large variety of environmental factors affecting the health and the behavior of the mothers and of the offspring in the early and later phases of development. Therefore, the experiments must be conducted under highly standardized conditions and must be controlled rigorously. It is concluded that the best experimental strategy for the evaluation of potential behavioral teratogens is not yet established. Therefore, it would be premature to decide on a fixed protocol to be included in routine animal safety experiments for drugs and other chemical substances.

Inhalation developmental toxicology studies: Teratology study of n-hexane in mice: Final report

Energy Technology Data Exchange (ETDEWEB)

Mast, T.J.; Decker, J.R.; Stoney, K.H.; Westerberg, R.B.; Evanoff, J.J.; Rommereim, R.L.; Weigel, R.J.

1988-05-01

Gestational exposure to n-hexane resulted in an increase in the number of resorbed fetuses for exposure groups relative to the control group; however, the increases were not directly correlated to exposure concentration. The differences were statistically significant for the 200-ppM with respect to total intrauterine death (early plus late resorptions), and with respect to late resorptions for the 5000-ppM group. A small, but statistically significant, reduction in female (but not male) fetal body weight relative to the control group was observed at the 5000-ppM exposure level. There were no exposure-related increases in any individual fetal malformation or variation, nor was there any increase in the incidence of combined malformations or variations. Gestational exposure of CD-1 mice to n-hexane vapors appeared to cause a degree of concentration-related developmental toxicity in the absence of overt maternal toxicity, but the test material was not found to be teratogenic. This developmental toxicity was manifested as an increase in the number of resorptions per litter for all exposure levels, and as a decrease in the uterine: extra-gestational weight gain ratio at the 5000-ppM exposure level. Because of the significant increase in the number of resorptions at the 200-ppM exposure level, a no observable effect level (NOEL) for developmental toxicity was not established for exposure of mice to 200, 1000 or 5000-ppM n-hexane vapors. 21 refs., 3 figs., 9 tabs.

Toxicology screen

Science.gov (United States)

... this page: //medlineplus.gov/ency/article/003578.htm Toxicology screen To use the sharing features on this page, please enable JavaScript. A toxicology screen refers to various tests that determine the ...

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

Science.gov (United States)

Grandjean, P

2015-12-01

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. © The Author(s) 2015.

Toxicology of metals and metalloids: Promising issues for future studies in environmental health and toxicology.

Science.gov (United States)

Barbosa, Fernando

2017-01-01

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.

Toxicology ontology perspectives.

Science.gov (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

2012-01-01

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.

Evidence-Based Toxicology.

Science.gov (United States)

Hoffmann, Sebastian; Hartung, Thomas; Stephens, Martin

Evidence-based toxicology (EBT) was introduced independently by two groups in 2005, in the context of toxicological risk assessment and causation as well as based on parallels between the evaluation of test methods in toxicology and evidence-based assessment of diagnostics tests in medicine. The role model of evidence-based medicine (EBM) motivated both proposals and guided the evolution of EBT, whereas especially systematic reviews and evidence quality assessment attract considerable attention in toxicology.Regarding test assessment, in the search of solutions for various problems related to validation, such as the imperfectness of the reference standard or the challenge to comprehensively evaluate tests, the field of Diagnostic Test Assessment (DTA) was identified as a potential resource. DTA being an EBM discipline, test method assessment/validation therefore became one of the main drivers spurring the development of EBT.In the context of pathway-based toxicology, EBT approaches, given their objectivity, transparency and consistency, have been proposed to be used for carrying out a (retrospective) mechanistic validation.In summary, implementation of more evidence-based approaches may provide the tools necessary to adapt the assessment/validation of toxicological test methods and testing strategies to face the challenges of toxicology in the twenty first century.

Forensic Toxicology: An Introduction.

Science.gov (United States)

Smith, Michael P; Bluth, Martin H

2016-12-01

This article presents an overview of forensic toxicology. The authors describe the three components that make up forensic toxicology: workplace drug testing, postmortem toxicology, and human performance toxicology. Also discussed are the specimens that are tested, the methods used, and how the results are interpreted in this particular discipline. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative analysis of perturbed molecular pathways identified in in vitro and in vivo toxicology studies

NARCIS (Netherlands)

Wiesinger, Martin; Mayer, Bernd; Jennings, Paul; Lukas, Arno

The development of in vitro toxicological testing strategies are hampered by the difficulty in extrapolation to the intact organism. Academic toxicological literature contains a wealth of mechanistically rich information, especially arising from omic studies, which could potentially be utilized to

Non-precautionary aspects of toxicology

International Nuclear Information System (INIS)

Grandjean, Philippe

2005-01-01

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

Radioactive 63Ni in biological research

International Nuclear Information System (INIS)

Kasprzak, K.S.; Sunderman, F.W. Jr.

1979-01-01

Applications of 63 Ni in biological research are reviewed, with emphasis upon recent investigations of nickel metabolism and toxicology in experimental animals. The radiochemistry of 63 Ni is summarized, including consideration of the preparation of certain 63 Ni compounds (e.g. 63 Ni(CO) 4 and 63 Ni 3 S 2 ) that are of current interest in toxicology, teratology and cancer research. Practical guidance is given regarding the detection and determination of 63 Ni in biological materials by autoradiography and liquid scintillation spectrometry. (author)

A history of the Teratology Society.

Science.gov (United States)

Shepard, T H; Barr, M; Brent, R L; Hendrickx, A; Kochhar, D; Oakley, G; Scott, W J

2000-11-01

The 39-year history of the Teratology Society is reviewed. An abbreviated history is outlined in table form, along with listings of the Warkany Lectures, the postgraduate courses, and officers of the Society. A year-by-year description of the events, including the scientific and social content of the annual meetings and changes in the business of the Society, is given, in many cases using comments from the past presidents. The valuable and unique diversity of the members is discussed and illustrated, presenting the disciplines and main research area of the presidents. The number of submitted abstracts and the various categories are tabulated, averaging the number and type over four periods. Within the past 10 years, a significant increase in the number of abstracts dealing with epidemiology and developmental biology is evident. The Society's development is compared with that of a human, and the question is asked: Have we reached the maturational stage of old age or senescence, or is the Society still maturing gracefully? This question needs further discussion by all the members. During the past 40 years, we have developed the scientific basis to prevent birth defects caused by rubella, alcoholism, and folate deficiency, as well as many other prenatal exposures. We must now engage in the political battles to obtain the resources needed to conduct further research and to implement the prevention programs, as well as to provide care and rehabilitation for persons with birth defects. Copyright 2000 Wiley-Liss, Inc.

TOXNET: Toxicology Data Network

Science.gov (United States)

... to TOXNET Your resource for searching databases on toxicology, hazardous chemicals, environmental health, and toxic releases SEARCH ... over 3,000 chemicals (1991-1998) Environmental Health & Toxicology Resources on environmental health and toxicology Visit Site ...

In honor of the Teratology Society's 50th anniversary: The role of Teratology Society members in the development and evolution of in vivo developmental toxicity test guidelines.

Science.gov (United States)

Tyl, Rochelle W

2010-06-01

Members of the Teratology Society (established in 1960) were involved in the first governmental developmental and reproductive toxicity testing guidelines (1966) by FDA following the thalidomide epidemic, followed by other national and international governmental testing guidelines. The Segment II (developmental toxicity) study design, described in rodents and rabbits, has evolved with additional enhanced endpoints and better descriptions, mechanistic insights, range-finding studies, and toxico/pharmacokinetic ADME information (especially for pharmaceuticals). Society members were also involved in the development of the current screening assays and tests for endocrine disruptors (beginning in 1996) and are now involved with developing new testing guidelines (e.g., the extended one-generation protocol), and evaluating the current test guidelines and new initiatives under ILSI/HESI sponsorship. New initiatives include ToxCast from the U.S. EPA to screen, prioritize, and predict toxic chemicals by high throughput and high-content in vitro assays, bioinformation, and modeling to reduce (or eliminate) in vivo whole animal studies. Our Society and its journal have played vital roles in the scientific and regulatory accomplishments in birth defects research over the past 50 years and will continue to do so in the future. Happy 50th anniversary! (c) 2010 Wiley-Liss, Inc.

History of Japanese Society of Toxicology.

Science.gov (United States)

Satoh, Tetsuo

2016-01-01

Founded in 1981, the Japanese Society of Toxicology (JSOT) has grown into an organization of nearly 3,000 members working together to advance the nation's scientific knowledge and understanding of toxicology through the implementation of planning that ensures a systematic and efficient expenditure of energies and resources, and is closely aligned with a strategy for accomplishing the Society's long-range plans. To promote public education in toxicology, the Society organizes public lectures during each year's annual meeting. Other activities include hosting scientific conferences, promoting continuing education, and facilitating international collaboration. Internally, the JSOT operates five standing committees: General Affairs, Educational, Editorial, Finance, and Science and Publicity to handle its necessary relationships. To bestow official recognition, the Society established its Toxicologist Certification Program in 1997, and has certified 536 members as Diplomat Toxicologists (DJSOT) as of May 1, 2016. Furthermore, on the same date, 43 JSOT members were certified as Emeritus Diplomats of the JSOT (EDJSOT). The Society has launched two official journals, the "Journal of Toxicological Sciences (JTS)" in 1981 and "Fundamental Toxicological Sciences (Fundam. Toxicol. Sci.)" in 2014. As for participation in the international organizations, the JSOT (then known as the Toxicological Research Group) joined the International Union of Toxicology as a charter member in 1980, and became a founding member of the Asian Society of Toxicology at its inauguration in 1994. Into the future, the JSOT will continue working diligently to advance knowledge and understanding of toxicology and secure its place among the interdisciplinary fields of science, humane studies, and ethics.

Paternal exposure and counselling: experience of a Teratology Information Service.

Science.gov (United States)

De Santis, Marco; Cesari, Elena; Cavaliere, Annafranca; Ligato, Maria Serena; Nobili, Elena; Visconti, Daniela; Caruso, Alessandro

2008-09-01

We describe paternal exposure and counselling in a selected population calling to an Italian Teratology Information Service (TIS). The majority of callers asked for paternal drug exposure (76%, drugs except chemotherapy) and treatment for cancer (17%, chemotherapy and/or radiotherapy). Others asked for exposure to diagnostic radiations (4%), recreational drugs (2%) and occupational chemicals (1%). Among paternal drugs neurological compounds, immunosuppressive drugs and antiviral agents were the main reasons for calling. In humans, there are no evidences of birth defects after paternal exposures, but to minimize any possible risk, counselling in men exposed to radio and chemotherapy should recommend delaying conception for at least 3 months after the end of the therapy. Male patients treated with drugs, whose teratogenic potential has been well assessed or suspected for maternal exposure, should be advised to practice effective birth control during therapy and up to one or two cycles of spermatogenesis and to avoid semen contact with vaginal walls during first trimester of pregnancy.

Predictive toxicology: the paths of the future

International Nuclear Information System (INIS)

Detilleux, Ph.; Vallier, L.; Legallais, C.; Leclerc, E.; Prot, J.M.; Choucha, L.; Baudoin, R.; Dufresne, M.; Gautier, A.; Carpentier, B.; Mansuy, D.; Pery, A.; Brochot, C.; Manivet, Ph.; Rabilloud, Th.; Spire, C.; Coumoul, X.; Junot, Ch.; Laprevote, O.; Le pape, A.; Le Guevel, R.; Tourneur, E.; Ben Mkaddem, S.; Chassin, C.; Aloulou, M.; Goujon, J.M.; Hertif, A.; Ouali, N.; Vimont, S.; Monteiro, R.; Rondeau, E.; Elbim, C.; Werts, C.; Vandewalle, A.; Ben Mkaddem, S.; Pedruzzi, E.; Coant, N.; Bens, M.; Cluzeaud, F.; Ogier-Denis, E.; Pongnimitprasert, N.; Babin-Chevaye, C.; Fay, M.; Bernard, M.; Dupuy, C.; Ei Benna, J.; Gougerot-Pocidale, M.A.; Braut-Boucher, F.; Pinton, Ph.; Lucioli, J.; Tsybulskyy, D.; Joly, B.; Laffitte, J.; Bourges-Abella, N.; Oswald, I.P.; Kolf-Clauw, M.; Pierre, St.; Bats, A.S.; Chevallier, A.; Bui, L.Ch.; Ambolet-Camoit, A.; Garlatti, M.; Aggerbeck, M.; Barouki, R.; Al Khansa, I.; Blanck, O.; Guillouzo, A.; Bars, R.; Rouas, C.; Bensoussan, H.; Suhard, D.; Tessier, C.; Grandcolas, L.; Pallardy, M.; Gueguen, Y.; Sparfel, L.; Pinel-Marie, M.L.; Boize, M.; Koscielny, S.; Desmots, S.; Pery, A.; Fardel, O.; Alvergnas, M.; Rouleau, A.; Lucchi, G.; Mantion, G.; Heyd, B.; Richert, L.; Ducoroy, P.; Martin, H.; Val, St.; Martinon, L.; Cachier, H.; Yahyaoui, A.; Marfaing, H.; Baeza-Squiban, A.; Martin-Chouly, C.; Bonvallet, M.; Morzadec, C.; Fardel, O.; Vernhet, L.; Baverel, G.; El Hage, M.; Nazaret, R.; Conjard-Duplany, A.; Ferrier, B.; Martin, G.; Legendre, A.; Desmots, S.; Lecomte, A.; Froment, P.; Habert, R.; Lemazurier, E.; Robinel, F.; Dupont, O.; Sanfins, E.; Dairou, J.; Chaffotte, A.F.; Busi, F.; Rodrigues Lima, F.; Dupret, J.M.; Mayati, A.; Le Ferrec, E.; Levoin, N.; Paris, H.; Uriac, Ph.; N'Diaye, M.; Lagadic-Gossmann, D.; Fardel, O.; Assemat, E.; Boublil, L.; Borot, M.C.; Marano, F.; Baeza-Squiban, A.; Martiny, V.Y.; Moroy, G.; Badel, A.; Miteva, M.A.; Hussain, S.; Ferecatu, I.; Borot, C.; Andreau, K.; Baeza-Squiban, A.; Marano, F.; Boland, S.; Leroux, M.; Zucchini-Pascal, N.; Peyre, L.; Rahmani, R.; Buron, N.; Porcedou, M.; Fromenty, B.; Borgne-Sanchez, A.; Rogue, A.; Spire, C.; Claude, N.; Guillouzo, A.

2010-01-01

Prevention of possible noxious effects in relation with the exposure to one or several chemical, physical or biological agents present in our domestic or professional environment is one of today's big public health stakes. Another stake is the better assessment of the risks linked with the use of health-care products. The efficacy and predictiveness of toxicology studies are directly related to the combination of alternate complementary methods and animal experiments (obtaining data from different species and with different models: in vitro, ex vivo and in vivo). Despite important efforts, the toxicological evaluation remains perfectible. The proceedings of this 2010 congress of the French Society of cell pharmaco-toxicology deal with recent advances, both scientific and technological, in 'predictive toxicology'. Four main topics are approached: cell and organ models, 'omics', in silico modeling, and new technologies (imaging, cell ships, high-speed processing). Among the different presentations, 3 abstracts present some recent advances in imaging techniques applied to toxicology studies. These are: 1 - first uses in toxicology of TOF-SIMS mass spectroscopy imaging (O. Laprevote, Paris-Descartes Univ. (FR)); 2 - Small animal imaging, a tool for predictive toxicology (A. Le Pape, CNRS Orleans (FR)); 3 - uranium localization at cell level using SIMS imaging technique (C. Rouas et al., IRSN Fontenay-aux-Roses (FR)). (J.S.)

Guidance on assessing the methodological and reporting quality of toxicologically relevant studies: A scoping review.

Science.gov (United States)

Samuel, Gbeminiyi O; Hoffmann, Sebastian; Wright, Robert A; Lalu, Manoj Mathew; Patlewicz, Grace; Becker, Richard A; DeGeorge, George L; Fergusson, Dean; Hartung, Thomas; Lewis, R Jeffrey; Stephens, Martin L

2016-01-01

Assessments of methodological and reporting quality are critical to adequately judging the credibility of a study's conclusions and to gauging its potential reproducibility. To aid those seeking to assess the methodological or reporting quality of studies relevant to toxicology, we conducted a scoping review of the available guidance with respect to four types of studies: in vivo and in vitro, (quantitative) structure-activity relationships ([Q]SARs), physico-chemical, and human observational studies. Our aims were to identify the available guidance in this diverse literature, briefly summarize each document, and distill the common elements of these documents for each study type. In general, we found considerable guidance for in vivo and human studies, but only one paper addressed in vitro studies exclusively. The guidance for (Q)SAR studies and physico-chemical studies was scant but authoritative. There was substantial overlap across guidance documents in the proposed criteria for both methodological and reporting quality. Some guidance documents address toxicology research directly, whereas others address preclinical research generally or clinical research and therefore may not be fully applicable to the toxicology context without some translation. Another challenge is the degree to which assessments of methodological quality in toxicology should focus on risk of bias - as in clinical medicine and healthcare - or be broadened to include other quality measures, such as confirming the identity of test substances prior to exposure. Our review is intended primarily for those in toxicology and risk assessment seeking an entry point into the extensive and diverse literature on methodological and reporting quality applicable to their work. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Expression analysis of some genes regulated by retinoic acid in controls and triadimefon-exposed embryos: is the amphibian Xenopus laevis a suitable model for gene-based comparative teratology?

Science.gov (United States)

Di Renzo, Francesca; Rossi, Federica; Bacchetta, Renato; Prati, Mariangela; Giavini, Erminio; Menegola, Elena

2011-06-01

The use of nonmammal models in teratological studies is a matter of debate and seems to be justified if the embryotoxic mechanism involves conserved processes. Published data on mammals and Xenopus laevis suggest that azoles are teratogenic by altering the endogenous concentration of retinoic acid (RA). The expression of some genes (Shh, Ptch-1, Gsc, and Msx2) controlled by retinoic acid is downregulated in rat embryos exposed at the phylotypic stage to the triazole triadimefon (FON). In order to propose X. laevis as a model for gene-based comparative teratology, this work evaluates the expression of Shh, Ptch-1, Gsc, and Msx2 in FON-exposed X. laevis embryos. Embryos, exposed to a high concentration level (500 µM) of FON from stage 13 till 17, were examined at stages 17, 27, and 47. Stage 17 and 27 embryos were processed to perform quantitative RT-PCR. The developmental rate was never affected by FON at any considered stage. FON-exposed stage 47 larvae showed the typical craniofacial malformations. A significant downregulation of Gsc was observed in FON-exposed stage 17 embryos. Shh, Ptch-1, Msx2 showed a high fluctuation of expression both in control and in FON-exposed samples both at stages 17 and 27. The downregulation of Gsc mimics the effects of FON on rat embryos, showing for this gene a common effect of FON in the two vertebrate classes. The high fluctuation observed in the gene expression of the other genes, however, suggests that X. laevis at this stage has limited utility for gene-based comparative teratology. © 2011 Wiley-Liss, Inc.

[Teratologic cranio-encephalic effects of chronic thinner inhalation in progenitors, in rats and humans].

Science.gov (United States)

Barroso-Moguel, R; Villeda-Hernández, J; Méndez-Armenta, M

1991-01-01

Inhalation of thinner by youngsters and adolescents is an increasing drug abuse problem in Mexico. It presents serious repercussions upon socio-economic, cultural, legal and health (neurologic and psychiatric) problems. We report a comparative study in humans and rats which demonstrate the embryotoxic and craneo encephalic teratologic effects in the children and brood of progenitors who have chronically inhaled thinner (in the case of pregnant women, before, at the beginning and throughout pregnancy). Inhaled thinner passes directly to the blood stream and crosses the placentary barrier freely reaching the embryo. It may cause craneal bone and partial or total encephalon agenesia, added to macro and microscopic lesions secondary to direct aggression to the neuroepithelial germ cells. Abortions and premature labor with weight and size underdeveloped products and placentary hemorrhages occur. Usually these die, but if they survive they show trascendental mental retardation, as well as neurologic and psychiatric sequels.

Aerospace Toxicology and Microbiology

Science.gov (United States)

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

2007-01-01

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.

Toxicología Vegetal

OpenAIRE

García Fernández, Antonio Juan

2010-01-01

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

78 FR 45253 - National Toxicology Program Scientific Advisory Committee on Alternative Toxicological Methods...

Science.gov (United States)

2013-07-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Toxicology Program... Alternative Methods (ICCVAM), the National Toxicology Program (NTP) Interagency Center for the Evaluation of... Director, National Toxicology Program. [FR Doc. 2013-17919 Filed 7-25-13; 8:45 am] BILLING CODE 4140-01-P ...

Toxicological evaluation of Cd-based fluorescent nanoprobes by means of in vivo studies

Science.gov (United States)

Farias, Patricia M. A.; Ma-Hock, Lan; Landsiedel, Robert; van Ravenzwaay, Bennard

2018-02-01

Cadmium still represents a stigma for many research- and/or industrial applications. Some deleterious effects are attributed to Cadmium. In the present work, highly fluorescent Cadmium sulfide quantum dots are investigated by e.g. physical-chemical characterization. Most important however is their application as fluorescent probes for bio-imaging in living cells and tissues. This work presents their toxicological evaluation by means of in vivo studies. Bio-imaging experiments are performed without any pre-treatment. The toxicological studies performed, strongly indicate that the use of Cadmium based nanoparticles as fluorescent probes may be nonhazardous and not induce side effects for cells/tissues.

Toxicology Education Foundation

Science.gov (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. ...

National Toxicology Program

Science.gov (United States)

... NTP? NTP develops and applies tools of modern toxicology and molecular biology to identify substances in the ... depend on for decisions that matter. The National Toxicology Program provides the scientific basis for programs, activities, ...

MicroRNAs and fetal brain development: Implications for ethanol teratology during the second trimester period of neurogenesis.

Directory of Open Access Journals (Sweden)

Rajesh eMiranda

2012-05-01

Full Text Available Maternal ethanol consumption during pregnancy can lead to a stereotypic cluster of fetal craniofacial, cardiovascular, skeletal and neurological deficits that are collectively termed the Fetal Alcohol Spectrum Disorder (FASD. Fetal ethanol exposure is a leading non-genetic cause of mental retardation. Mechanisms underlying the etiology of ethanol teratology are varied and complex. This review will focus on the developing brain as an important and vulnerable ethanol target. Near the end of the first trimester, and during the second trimester, fetal neural stem cells (NSCs produce most of the neurons of the adult brain, and ethanol has been shown to influence NSC renewal and maturation. We will discuss the neural developmental and teratological implications of the biogenesis and function of microRNAs (miRNAs, a class of small non-protein-coding RNAs that control the expression of gene networks by translation repression. A small but growing body of research has identified ethanol-sensitive miRNAs at different stages of NSC and brain maturation. While many microRNAs appear to be vulnerable to ethanol at specific developmental stages, a few, like the miR-9 family, appear to exhibit broad vulnerability to ethanol across multiple stages of NSC differentiation. An assessment of the regulation and function of these miRNAs provides important clues about the mechanisms that underlie fetal vulnerability to alterations in the maternal-fetal environment and yields insights into the genesis of FASD.

EUROPEAN TERATOLOGY INFORMATION SERVICE: EXPERIENCE, PROBLEMS AND PERSPECTIVES

Directory of Open Access Journals (Sweden)

A.V. Ostrovskaya

2007-01-01

Full Text Available Congenital malformations are still the important medical and social issue. They take the second place among the reasons for the infant mortality and cause up to 18,3% of disablement cases among the children. Exogenous factors, effecting the growing fetus, are very essential along with the genetic matters among the reasons for the congenital malformations. The importance of information on the teratogenic potential of the medications is acknowledged by the doctors from various countries. The article outlines the information on entis activity — European network of teratology information services — a non profit organization, rendering consulting services to the pregnant women and medical staff, regarding the embryo and fetotoxic actions of the medications. The authors highlight the history of entis, its objectives, principles of operation and consulting algorithm and list the basic scientific publications by the entis members for the recent years. The article deals with the most obvious problems, which the organization members face, first of all — the quality of the information they receive. The authors also provide the substantiation for the necessity to develop such an information service in Russia and express hope for the successful development of the entis subsidiary they formed in Moscow.Key words: congenital malformations, medications, pregnancy, embryotoxicity.

Emerging approaches in predictive toxicology.

Science.gov (United States)

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

2014-12-01

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. © 2014 Wiley Periodicals, Inc.

Advancing Toxicology Research Using In Vivo High Throughput Toxicology with Small Fish Models

Science.gov (United States)

Planchart, Antonio; Mattingly, Carolyn J.; Allen, David; Ceger, Patricia; Casey, Warren; Hinton, David; Kanungo, Jyotshna; Kullman, Seth W.; Tal, Tamara; Bondesson, Maria; Burgess, Shawn M.; Sullivan, Con; Kim, Carol; Behl, Mamta; Padilla, Stephanie; Reif, David M.; Tanguay, Robert L.; Hamm, Jon

2017-01-01

Summary Small freshwater fish models, especially zebrafish, offer advantages over traditional rodent models, including low maintenance and husbandry costs, high fecundity, genetic diversity, physiology similar to that of traditional biomedical models, and reduced animal welfare concerns. The Collaborative Workshop on Aquatic Models and 21st Century Toxicology was held at North Carolina State University on May 5-6, 2014, in Raleigh, North Carolina, USA. Participants discussed the ways in which small fish are being used as models to screen toxicants and understand mechanisms of toxicity. Workshop participants agreed that the lack of standardized protocols is an impediment to broader acceptance of these models, whereas development of standardized protocols, validation, and subsequent regulatory acceptance would facilitate greater usage. Given the advantages and increasing application of small fish models, there was widespread interest in follow-up workshops to review and discuss developments in their use. In this article, we summarize the recommendations formulated by workshop participants to enhance the utility of small fish species in toxicology studies, as well as many of the advances in the field of toxicology that resulted from using small fish species, including advances in developmental toxicology, cardiovascular toxicology, neurotoxicology, and immunotoxicology. We also review many emerging issues that will benefit from using small fish species, especially zebrafish, and new technologies that will enable using these organisms to yield results unprecedented in their information content to better understand how toxicants affect development and health. PMID:27328013

ACToR-AGGREGATED COMPUTATIONAL TOXICOLOGY ...

Science.gov (United States)

One goal of the field of computational toxicology is to predict chemical toxicity by combining computer models with biological and toxicological data. predict chemical toxicity by combining computer models with biological and toxicological data

Progress in computational toxicology.

Science.gov (United States)

Ekins, Sean

2014-01-01

Computational methods have been widely applied to toxicology across pharmaceutical, consumer product and environmental fields over the past decade. Progress in computational toxicology is now reviewed. A literature review was performed on computational models for hepatotoxicity (e.g. for drug-induced liver injury (DILI)), cardiotoxicity, renal toxicity and genotoxicity. In addition various publications have been highlighted that use machine learning methods. Several computational toxicology model datasets from past publications were used to compare Bayesian and Support Vector Machine (SVM) learning methods. The increasing amounts of data for defined toxicology endpoints have enabled machine learning models that have been increasingly used for predictions. It is shown that across many different models Bayesian and SVM perform similarly based on cross validation data. Considerable progress has been made in computational toxicology in a decade in both model development and availability of larger scale or 'big data' models. The future efforts in toxicology data generation will likely provide us with hundreds of thousands of compounds that are readily accessible for machine learning models. These models will cover relevant chemistry space for pharmaceutical, consumer product and environmental applications. Copyright © 2013 Elsevier Inc. All rights reserved.

Analysis of Statistical Methods Currently used in Toxicology Journals.

Science.gov (United States)

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

2014-09-01

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.

[Clinical toxicology of the Academy: yesterday, today and tomorrow].

Science.gov (United States)

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

2013-12-01

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.

Environmental Toxicology Research Facility

Data.gov (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...

21 CFR 862.3200 - Clinical toxicology calibrator.

Science.gov (United States)

2010-04-01

... 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 is...

Techniques for Investigating Molecular Toxicology of Nanomaterials.

Science.gov (United States)

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

2016-06-01

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.

Mass Spectrometry Applications for Toxicology

OpenAIRE

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

2016-01-01

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 i...

Handbook of systems toxicology

National Research Council Canada - National Science Library

Casciano, Daniel A; Sahu, Saura C

2011-01-01

"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...

42 CFR 493.937 - Toxicology.

Science.gov (United States)

2010-10-01

... 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 must...

Systems toxicology: applications of toxicogenomics, transcriptomics, proteomics and metabolomics in toxicology

NARCIS (Netherlands)

Heijne, W.H.M.; Kienhuis, A.S.; Ommen, van B.; Stierum, R.; Groten, J.P.

2005-01-01

Toxicogenomics can facilitate the identification and characterization of toxicity, as illustrated in this review. Toxicogenomics, the application of the functional genomics technologies (transcriptomics, proteomics and metabolomics) in toxicology enables the study of adverse effects of xenobiotic

Toxicological awakenings: the rebirth of hormesis as a central pillar of toxicology

International Nuclear Information System (INIS)

Calabrese, Edward J.

2005-01-01

This paper assesses historical reasons that may account for the marginalization of hormesis as a dose-response model in the biomedical sciences in general and toxicology in particular. The most significant and enduring explanatory factors are the early and close association of the concept of hormesis with the highly controversial medical practice of homeopathy and the difficulty in assessing hormesis with high-dose testing protocols which have dominated the discipline of toxicology, especially regulatory toxicology. The long-standing and intensely acrimonious conflict between homeopathy and 'traditional' medicine (allopathy) lead to the exclusion of the hormesis concept from a vast array of medical- and public health-related activities including research, teaching, grant funding, publishing, professional societal meetings, and regulatory initiatives of governmental agencies and their advisory bodies. Recent publications indicate that the hormetic dose-response is far more common and fundamental than the dose-response models [threshold/linear no threshold (LNT)] used in toxicology and risk assessment, and by governmental regulatory agencies in the establishment of exposure standards for workers and the general public. Acceptance of the possibility of hormesis has the potential to profoundly affect the practice of toxicology and risk assessment, especially with respect to carcinogen assessment

COMPUTATIONAL TOXICOLOGY-WHERE IS THE DATA? ...

Science.gov (United States)

This talk will briefly describe the state of the data world for computational toxicology and one approach to improve the situation, called ACToR (Aggregated Computational Toxicology Resource). This talk will briefly describe the state of the data world for computational toxicology and one approach to improve the situation, called ACToR (Aggregated Computational Toxicology Resource).

In silico toxicology protocols.

Science.gov (United States)

Myatt, Glenn J; Ahlberg, Ernst; Akahori, Yumi; Allen, David; Amberg, Alexander; Anger, Lennart T; Aptula, Aynur; Auerbach, Scott; Beilke, Lisa; Bellion, Phillip; Benigni, Romualdo; Bercu, Joel; Booth, Ewan D; Bower, Dave; Brigo, Alessandro; Burden, Natalie; Cammerer, Zoryana; Cronin, Mark T D; Cross, Kevin P; Custer, Laura; Dettwiler, Magdalena; Dobo, Krista; Ford, Kevin A; Fortin, Marie C; Gad-McDonald, Samantha E; Gellatly, Nichola; Gervais, Véronique; Glover, Kyle P; Glowienke, Susanne; Van Gompel, Jacky; Gutsell, Steve; Hardy, Barry; Harvey, James S; Hillegass, Jedd; Honma, Masamitsu; Hsieh, Jui-Hua; Hsu, Chia-Wen; Hughes, Kathy; Johnson, Candice; Jolly, Robert; Jones, David; Kemper, Ray; Kenyon, Michelle O; Kim, Marlene T; Kruhlak, Naomi L; Kulkarni, Sunil A; Kümmerer, Klaus; Leavitt, Penny; Majer, Bernhard; Masten, Scott; Miller, Scott; Moser, Janet; Mumtaz, Moiz; Muster, Wolfgang; Neilson, Louise; Oprea, Tudor I; Patlewicz, Grace; Paulino, Alexandre; Lo Piparo, Elena; Powley, Mark; Quigley, Donald P; Reddy, M Vijayaraj; Richarz, Andrea-Nicole; Ruiz, Patricia; Schilter, Benoit; Serafimova, Rositsa; Simpson, Wendy; Stavitskaya, Lidiya; Stidl, Reinhard; Suarez-Rodriguez, Diana; Szabo, David T; Teasdale, Andrew; Trejo-Martin, Alejandra; Valentin, Jean-Pierre; Vuorinen, Anna; Wall, Brian A; Watts, Pete; White, Angela T; Wichard, Joerg; Witt, Kristine L; Woolley, Adam; Woolley, David; Zwickl, Craig; Hasselgren, Catrin

2018-04-17

The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information. Copyright © 2018. Published by Elsevier Inc.

Postmortem aviation forensic toxicology: an overview.

Science.gov (United States)

Chaturvedi, Arvind K

2010-05-01

An overview of the subtopic aviation combustion toxicology of the field of aerospace toxicology has been published. In a continuation of the overview, the findings associated with postmortem aviation forensic toxicology are being summarized in the present overview. A literature search for the period of 1960-2007 was performed. The important findings related to postmortem toxicology were evaluated. In addition to a brief introduction, this overview is divided into the sections of analytical methods; carboxyhemoglobin and blood cyanide ion; ethanol; drugs; result interpretation; glucose and hemoglobin A(1c); and references. Specific details of the subject matter were discussed. It is anticipated that this overview will be an outline source for aviation forensic toxicology within the field of aerospace toxicology.

Biology Division progress report, June 1, 1980-July 31, 1982

Energy Technology Data Exchange (ETDEWEB)

1982-12-01

Highlights of progress for the period June 1980 through July 1982 are summarized. Discussions of projects are presented under the following headings: molecular and cellular sciences; cellular and comparative mutagenesis; mammalian genetics and teratology; toxicology; and carcinogenesis. In addition this report includes an outline of educational activities. Separate abstracts have been prepared for individual technical reports for inclusion in the Energy Data Base. (RJC)

Toxicology Study No. S.0024589d 15, Human Cell Line Activation Test of the Novel Energetic, 3,4 -Dinitropyrazole (DNP)

Science.gov (United States)

2016-04-01

Assay 1 0.259 0.278 Assay 2 0.299 6.3 CD54 and CD86 expression in response to DNP exposure of THP -1 cells Three independent tests were...2 Toxicology Study No. S.0024589d-15, April 2016 Toxicology Directorate Human Cell Line Activation Test of the Novel Energetic 3,4...report. 17-05-2016 Technical Report March 2016-April 2016 Toxicology Study No. S.0024589d-15 Human Cell Line Activation Test of the Novel

Toxicological risks of selected flame-retardant chemicals

National Research Council Canada - National Science Library

2000-01-01

... Committee on Toxicology Board on Environmental Studies and Toxicology Commission on Life Sciences National Research Council NATIONAL ACADEMY PRESS Washington, D.C. i Copyrighttrue Please breaks inserted. are Page files. accidentally typesetting been have may original from the errors not typographic original retained, and from the created ca...

Toxicological Risks of Selected Flame-Retardant Chemicals

National Research Council Canada - National Science Library

2000-01-01

... Committee on Toxicology Board on Environmental Studies and Toxicology Commission on Life Sciences National Research Council NATIONAL ACADEMY PRESS Washington, D.C. i Copyrighttrue Please breaks inserted. are Page files. accidentally typesetting been have may original from the errors not typographic original retained, and from the created ca...

Fossil fuel toxicology

International Nuclear Information System (INIS)

Anon.

1976-01-01

A program is described for the investigation of the toxicology of coal-derived effluents that will utilize a battery of cellular and mammalian test systems and end points to evaluate the toxicological effects of acute, sub-acute, and long-term, low-level exposure to gaseous and particulate effluents from combustion of coal, with special emphasis on fluidized bed combustion

Toxicological study of the hepatotherapeutic herbal formula, Chunggan extract, in beagle dogs

Institute of Scientific and Technical Information of China (English)

Woo-Jin Choi; Hwa-Seung Yoo; Yeon-Weol Lee; Chang-Gue Son; Jang-Woo Shin; Jin-Young Son; Dong-Seok Seo; Hark-Soo Park; Seung-Hyun Han; Ha-Jung Sung; Jung-Hyo Cho; Chong-Kwan Cho

2006-01-01

AIM: To evaluate the pharmaceutical safety of a Chinese herbal formula, Chunggan extract (CGX), traditionally prescribed as a hepatotherapeutic drug via systemic acute and subacute toxicological study.METHODS: Twenty male dogs and 20 female dogs were fed doses 50 times and 4 times greater than the clinically-recommended drug dosages in an acute and a subacute toxicological study, respectively. Adverse effects were examined by comparing the differences between normal and drug-administered groups using clinical signs, necropsies, histopathologic findings, haematology,urinalysis, and biochemical analysis.RESULTS: In the acute study no change in the body weight, diarrhoea, apetite, mortality rate and histopathology of major organs was observed in male or female dogs with a single administration of CGX at 5 g/kg. No drug-induced abnormalities at analysis of histopathology,haematology, urinalysis, and biochemistry were found with any dose of this drug.CONCLUSION: CGX is supposed to be very safe when used in a clinical application with a wide therapeutic index.

A Prospective Observation Study of Medical Toxicology Consultation in a U.S. Combat Theater.

Science.gov (United States)

Maddry, Joseph K; Ng, Patrick C; Sessions, Daniel; Bebarta, Vikhyat S

2016-11-01

Since 2001, U.S. military personnel and active duty, uniformed physicians providing medical support have been deployed to Afghanistan. Medical toxicologists are among the physicians deployed. There is a paucity of information present in the literature that has documented cases treated by toxicologists in theater. This prospective observational study describes 15 male patients treated in theater by a military medical toxicologist. We performed a prospective observational study in which a medical toxicologist consulted and reported on deployed toxicology cases occurring during a 5-month deployment to Bagram, Afghanistan. Fifteen toxicology cases were collected during the 5-month period. The patients included three Afghan civilians, three U.S. civilians, and nine U.S. military personnel. Eight cases were attempts at recreational euphoria, two were self-harm attempts, two were from performance-enhancing supplements, two were accidental occupational exposures and one was alcohol withdrawal. Methanol was the most common exposure followed by dextromethorphan, supplements, opiates, and chlorine gas. In our study, we found that toxic alcohols and nonprescription medications were the most common exposures. In addition, this is the first study to describe bedside toxicology consults for U.S. combat forces in theater and the use of an observation unit for critically ill patients. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

Teratology Public Affairs Committee position paper: maternal obesity and pregnancy.

Science.gov (United States)

Scialli, Anthony R

2006-02-01

Compared to normal-weight women, obese women have an increased risk of infertility and pregnancy complications. The most consistently described pregnancy complications are hypertensive disorders, gestational diabetes mellitus, thromboembolic events, and cesarean section. Fetal and neonatal complications may include congenital malformations, macrosomia, and shoulder dystocia. The literature suggests that women with a body mass index (BMI) >or=30 have approximately double the risk of having a child with a neural tube defect (NTD) compared to normal-weight women, and the increased risk associated with higher maternal body weight does not appear to be modified by folic acid supplementation. The Public Affairs Committee of the Teratology Society supports the public health initiatives identified by the U.S. Food and Drug Administration in 2004 and the research initiatives identified by the National Institutes of Health in 2004. The Public Affairs Committee recommends that clinicians counsel women about appropriate caloric intake and exercise and that health-care providers educate parents about appropriate childhood nutrition. Breast-feeding should be encouraged based on evidence of a protective effect against childhood obesity, as well as other health advantages. Birth Defects Research (Part A), 2006. (c) 2006 Wiley-Liss, Inc.

Phytochemical, toxicological and histo-pathological studies of some ...

African Journals Online (AJOL)

The plants therefore possess some important biological activities that could be harnessed and employed beneficially in the management of viral and bacterial infections. Keywords: Phytochemistry; toxicology; histo-pathology; rat; medicinal plants; Nigeria International Journal of Natural and Applied Sciences Vol. 2 (3) 2006: ...

Occupational medicine and toxicology

Directory of Open Access Journals (Sweden)

Fischer Axel

2006-02-01

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.

Agenda of behavioral toxicology

Energy Technology Data Exchange (ETDEWEB)

Weiss, B

1978-01-01

The author describes behavioral toxicology as a new discipline and contrasts it to the fields of physics and pharmacology. Several questions are raised and discussed concerning the field of behavioral toxicology. Some of these questions are: (1) how is an adverse behavioral effect recognized; (2) how can the non-specific be specified; (3) are standardized test batteries feasible. The problem of chronic intake is discussed as well as drawing information from other related disciplines such as neurochemistry, neuropathology and neurophysiology. The author concludes with several statements concerning new directions in the discipline of behavioral toxicology.

High Throughput Transcriptomics @ USEPA (Toxicology ...

Science.gov (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. Responses should ideally be translated into tissue-, organ-, and organism-level effects. It must be economical and scalable. Using a High Throughput Transcriptomics platform within US EPA provides broader coverage of biological activity space and toxicological MOAs and helps fill the toxicological data gap. Slide presentation at the 2016 ToxForum on using High Throughput Transcriptomics at US EPA for broader coverage biological activity space and toxicological MOAs.

Summary introduction to environmental toxicology

International Nuclear Information System (INIS)

Heinzow, B.; Jessen, H.; Wendorff, D.

1986-01-01

The increasing environmental consciousness and the increasing public interest in environmental medicine and toxicology is much appreciated by the Research Institute for Environmental Toxicology. This information brochure gives the reader some insight into the importance of environmental toxicology and into the waste of the Research Institute. In response to the current situation, the authors have included an appendix on radiation protection. (orig./PW) [de

The Emergence of Systematic Review in Toxicology.

Science.gov (United States)

Stephens, Martin L; Betts, Kellyn; Beck, Nancy B; Cogliano, Vincent; Dickersin, Kay; Fitzpatrick, Suzanne; Freeman, James; Gray, George; Hartung, Thomas; McPartland, Jennifer; Rooney, Andrew A; Scherer, Roberta W; Verloo, Didier; Hoffmann, Sebastian

2016-07-01

The Evidence-based Toxicology Collaboration hosted a workshop on "The Emergence of Systematic Review and Related Evidence-based Approaches in Toxicology," on November 21, 2014 in Baltimore, Maryland. The workshop featured speakers from agencies and organizations applying systematic review approaches to questions in toxicology, speakers with experience in conducting systematic reviews in medicine and healthcare, and stakeholders in industry, government, academia, and non-governmental organizations. Based on the workshop presentations and discussion, here we address the state of systematic review methods in toxicology, historical antecedents in both medicine and toxicology, challenges to the translation of systematic review from medicine to toxicology, and thoughts on the way forward. We conclude with a recommendation that as various agencies and organizations adapt systematic review methods, they continue to work together to ensure that there is a harmonized process for how the basic elements of systematic review methods are applied in toxicology. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

Toxicology: a discipline in need of academic anchoring--the point of view of the German Society of Toxicology.

Science.gov (United States)

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

2015-10-01

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.

Advancing Risk Assessment through the Application of Systems Toxicology

Science.gov (United States)

Sauer, John Michael; Kleensang, André; Peitsch, Manuel C.; Hayes, A. Wallace

2016-01-01

Risk assessment is the process of quantifying the probability of a harmful effect to individuals or populations from human activities. Mechanistic approaches to risk assessment have been generally referred to as systems toxicology. Systems toxicology makes use of advanced analytical and computational tools to integrate classical toxicology and quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Three presentations including two case studies involving both in vitro and in vivo approaches described the current state of systems toxicology and the potential for its future application in chemical risk assessment. PMID:26977253

42 CFR 493.1213 - Condition: Toxicology.

Science.gov (United States)

2010-10-01

... 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, the...

Toxicology in Asia--Past, present, and future.

Science.gov (United States)

Satoh, T

2015-12-01

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. © The Author(s) 2015.

Toxicología clínica comunitaria Community Clinical Toxicology

Directory of Open Access Journals (Sweden)

María Elena Leal

2011-08-01

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

TOXICOLOGICAL RESEARCH INVOLVING HUMANS: ETHICAL AND REGULATORY CONSIDERATIONS

Science.gov (United States)

This paper discusses the need for the Society of Toxicology (SOT) to develop a policy for ethical research in humans, and a review for publication of these studies. Observations on human beings have been the foundation upon which toxicologic knowledge has been built since the in...

The Global Educational Toxicology Uniting Project (GETUP): an Analysis of the First Year of a Novel Toxicology Education Project.

Science.gov (United States)

Wong, Anselm; Vohra, Rais; Ruha, Anne-Michelle; Koutsogiannis, Zeff; Graeme, Kimberlie; Dargan, Paul I; Wood, David M; Greene, Shaun L

2015-09-01

The international boundaries to medical education are becoming less marked as new technologies such as multiuser videoconferencing are developed and become more accessible to help bridge the communication gaps. The Global Educational Toxicology Uniting Project (GETUP) is aimed at connecting clinicians in countries with established clinical toxicology services to clinicians in countries without clinical toxicologists around the globe. Centers that manage or consult on toxicology cases were registered through the American College of Medical Toxicology website via Survey Monkey®. Data was analyzed retrospectively from February 2014 to January 2015. Google hangouts® was used as the main conferencing software, but some sites preferred the use of Skype®. Registration data included contact details and toxicology background and qualifications. Thirty sites in 19 different countries in Australasia, Europe, Africa, and America were registered. Twenty-eight (93 %) sites were located in a major urban center, one (3.5 %) site in a major rural center and one (3.5 %) a private practice. Expectations of GETUP included sharing toxicology cases and education (30, 100 % of sites), assistance with toxicology management guidelines (2, 7 %), assistance with providing a toxicology teaching curriculum in languages other than English (2, 7 %), and managing toxicology presentations in resource-poor settings, international collaboration, and toxicovigilance (2 sites, 7 %). Twenty-two conferences were performed during the first 12 months with a mean of 3 cases per conference. GETUP has connected countries and clinical units with and without toxicology services and will provide a platform to improve international collaboration in clinical toxicology.

Size Distributions and Characterization of Native and Ground Samples for Toxicology Studies

Science.gov (United States)

McKay, David S.; Cooper, Bonnie L.; Taylor, Larry A.

2010-01-01

This slide presentation shows charts and graphs that review the particle size distribution and characterization of natural and ground samples for toxicology studies. There are graphs which show the volume distribution versus the number distribution for natural occurring dust, jet mill ground dust, and ball mill ground dust.

Africa's present and future needs in toxicology education: Southern African perspective

International Nuclear Information System (INIS)

Gulumian, Mary; Ginsburg, Carren; Stewart, Michael J.

2005-01-01

Degrees and diplomas as well as certificates that are granted by universities and technikons in South Africa in scientific disciplines, such as forensic medicine, pharmacology, marine and veterinary sciences, environmental health, and occupational hygiene, include toxicology as one of the subjects in their overall syllabus. However, aspects of toxicology included in each of these courses are biased towards that particular subdiscipline and basic level of toxicology may be taught. Educational needs in toxicology in South Africa can be summarized as follows: (a) recognition of toxicology as a discipline in its own right at these tertiary education institutions and (b) creation of opportunities to study and obtain higher degrees in one or more of the many subdisciplines of toxicology. The results from a survey conducted on the toxicology syllabi offered at these tertiary education institutions are used to substantiate these needs

Translational toxicology: a developmental focus for integrated research strategies.

Science.gov (United States)

Hughes, Claude; Waters, Michael; Allen, David; Obasanjo, Iyabo

2013-09-30

Given that toxicology studies the potential adverse effects of environmental exposures on various forms of life and that clinical toxicology typically focuses on human health effects, what can and should the relatively new term of "translational toxicology" be taken to mean? Our assertion is that the core concept of translational toxicology must incorporate existing principles of toxicology and epidemiology, but be driven by the aim of developing safe and effective interventions beyond simple reduction or avoidance of exposure to prevent, mitigate or reverse adverse human health effects of exposures.The field of toxicology has now reached a point where advances in multiple areas of biomedical research and information technologies empower us to make fundamental transitions in directly impacting human health. Translational toxicology must encompass four action elements as follows: 1) Assessing human exposures in critical windows across the lifespan; 2) Defining modes of action and relevance of data from animal models; 3) Use of mathematical models to develop plausible predictions as the basis for: 4) Protective and restorative human health interventions. The discussion focuses on the critical window of in-utero development. Exposure assessment, basic toxicology and development of certain categories of mathematical models are not new areas of research; however overtly integrating these in order to conceive, assess and validate effective interventions to mitigate or reverse adverse effects of environmental exposures is our novel opportunity. This is what we should do in translational toxicology so that we have a portfolio of interventional options to improve human health that include both minimizing exposures and specific preventative/restorative/mitigative therapeutics.

Regulatory issues in accreditation of toxicology laboratories.

Science.gov (United States)

Bissell, Michael G

2012-09-01

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.

The underlying toxicological mechanism of chemical mixtures: A case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum

International Nuclear Information System (INIS)

Tian, Dayong; Lin, Zhifen; Zhou, Xianghong; Yin, Daqiang

2013-01-01

Intracellular chemical reaction of chemical mixtures is one of the main reasons that cause synergistic or antagonistic effects. However, it still remains unclear what the influencing factors on the intracellular chemical reaction are, and how they influence on the toxicological mechanism of chemical mixtures. To reveal this underlying toxicological mechanism of chemical mixtures, a case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum was employed, and both their joint effects and mixture toxicity were observed. Then series of two-step linear regressions were performed to describe the relationships between joint effects, the expected additive toxicities and descriptors of individual chemicals (including concentrations, binding affinity to receptors, octanol/water partition coefficients). Based on the quantitative relationships, the underlying joint toxicological mechanisms were revealed. The result shows that, for mixtures with their joint effects resulting from intracellular chemical reaction, their underlying toxicological mechanism depends on not only their interaction with target proteins, but also their transmembrane actions and their concentrations. In addition, two generic points of toxicological mechanism were proposed including the influencing factors on intracellular chemical reaction and the difference of the toxicological mechanism between single reactive chemicals and their mixtures. This study provided an insight into the understanding of the underlying toxicological mechanism for chemical mixtures with intracellular chemical reaction. - Highlights: • Joint effects of nitriles and aldehydes at non-equitoxic ratios were determined. • A novel descriptor, ligand–receptor interaction energy (E binding ), was employed. • Quantitative relationships for mixtures were developed based on a novel descriptor. • The underlying toxic mechanism was revealed based on quantitative relationships. • Two generic

The underlying toxicological mechanism of chemical mixtures: A case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum

Energy Technology Data Exchange (ETDEWEB)

Tian, Dayong [State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092 (China); Department of Chemical and Environmental Engineering, Anyang Institute of Technology, Anyang 455000 (China); Lin, Zhifen, E-mail: lzhifen@tongji.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092 (China); Zhou, Xianghong [Department of Public Management, Tongji University, Shanghai 200092 (China); Yin, Daqiang [Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092 (China)

2013-10-15

Intracellular chemical reaction of chemical mixtures is one of the main reasons that cause synergistic or antagonistic effects. However, it still remains unclear what the influencing factors on the intracellular chemical reaction are, and how they influence on the toxicological mechanism of chemical mixtures. To reveal this underlying toxicological mechanism of chemical mixtures, a case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum was employed, and both their joint effects and mixture toxicity were observed. Then series of two-step linear regressions were performed to describe the relationships between joint effects, the expected additive toxicities and descriptors of individual chemicals (including concentrations, binding affinity to receptors, octanol/water partition coefficients). Based on the quantitative relationships, the underlying joint toxicological mechanisms were revealed. The result shows that, for mixtures with their joint effects resulting from intracellular chemical reaction, their underlying toxicological mechanism depends on not only their interaction with target proteins, but also their transmembrane actions and their concentrations. In addition, two generic points of toxicological mechanism were proposed including the influencing factors on intracellular chemical reaction and the difference of the toxicological mechanism between single reactive chemicals and their mixtures. This study provided an insight into the understanding of the underlying toxicological mechanism for chemical mixtures with intracellular chemical reaction. - Highlights: • Joint effects of nitriles and aldehydes at non-equitoxic ratios were determined. • A novel descriptor, ligand–receptor interaction energy (E{sub binding}), was employed. • Quantitative relationships for mixtures were developed based on a novel descriptor. • The underlying toxic mechanism was revealed based on quantitative relationships. • Two

[Development and Application of Metabonomics in Forensic Toxicology].

Science.gov (United States)

Yan, Hui; Shen, Min

2015-06-01

Metabonomics is an important branch of system biology following the development of genomics, transcriptomics and proteomics. It can perform high-throughput detection and data processing with multiple parameters, potentially enabling the identification and quantification of all small metabolites in a biological system. It can be used to provide comprehensive information on the toxicity effects, toxicological mechanisms and biomarkers, sensitively finding the unusual metabolic changes caused by poison. This article mainly reviews application of metabonomics in toxicological studies of abused drugs, pesticides, poisonous plants and poisonous animals, and also illustrates the new direction of forensic toxicology research.

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

Science.gov (United States)

Hoenerhoff, Mark J; Hartke, James

2015-01-01

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. © 2014 by The Author(s).

Predictive Toxicology: Current Status and Future Outlook (EBI ...

Science.gov (United States)

Slide presentation at the EBI-EMBL Industry Programme Workshop on Predictive Toxicology and the currently status of Computational Toxicology activities at the US EPA. Slide presentation at the EBI-EMBL Industry Programme Workshop on Predictive Toxicology and the currently status of Computational Toxicology activities at the US EPA.

Toxicological profile for uranium. Final report

International Nuclear Information System (INIS)

1990-12-01

The ATSDR Toxicological Profile for Uranium is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substances's toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

Toxicological profile for radon. Final report

International Nuclear Information System (INIS)

1990-12-01

The ATSDR Toxicological Profile for Radon is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substance's toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

Toxicological profile for plutonium. Final report

International Nuclear Information System (INIS)

1990-12-01

The ATSDR Toxicological Profile for Plutonium is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substance's toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

Toxicological profile for radium. Final report

International Nuclear Information System (INIS)

1990-12-01

The ATSDR Toxicological Profile for Radium is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substances' toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

Toxicology and Epidemiology: Improving the Science with a Framework for Combining Toxicological and Epidemiological Evidence to Establish Causal Inference

Science.gov (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.

2011-01-01

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. PMID:21561883

The four cornerstones of Evolutionary Toxicology.

Science.gov (United States)

Bickham, John W

2011-05-01

Evolutionary Toxicology is the study of the effects of chemical pollutants on the genetics of natural populations. Research in Evolutionary Toxicology uses experimental designs familiar to the ecotoxicologist with matched reference and contaminated sites and the selection of sentinel species. It uses the methods of molecular genetics and population genetics, and is based on the theories and concepts of evolutionary biology and conservation genetics. Although it is a relatively young field, interest is rapidly growing among ecotoxicologists and more and more field studies and even controlled laboratory experiments are appearing in the literature. A number of population genetic impacts have been observed in organisms exposed to pollutants which I refer to here as the four cornerstones of Evolutionary Toxicology. These include (1) genome-wide changes in genetic diversity, (2) changes in allelic or genotypic frequencies caused by contaminant-induced selection acting at survivorship loci, (3) changes in dispersal patterns or gene flow which alter the genetic relationships among populations, and (4) changes in allelic or genotypic frequencies caused by increased mutation rates. It is concluded that population genetic impacts of pollution exposure are emergent effects that are not necessarily predictable from the mode of toxicity of the pollutant. Thus, to attribute an effect to a particular contaminant requires a careful experimental design which includes selection of appropriate reference sites, detailed chemistry analyses of environmental samples and tissues, and the use of appropriate biomarkers to establish exposure and effect. This paper describes the field of Evolutionary Toxicology and discusses relevant field studies and their findings. © Springer Science+Business Media, LLC 2011

Latin America's present and future challenges in toxicology education

International Nuclear Information System (INIS)

Rojas, M.

2005-01-01

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

Impact of online toxicology training on health professionals: the Global Educational Toxicology Uniting Project (GETUP).

Science.gov (United States)

Wong, Anselm; Vohra, Rais; Dawson, Andrew H; Stolbach, Andrew

2017-11-01

The Global Educational Toxicology Uniting Project (GETUP), supported by the American College of Medical Toxicology, links countries with and without toxicology services via distance education with the aim to improve education. Due to the lack of toxicology services in some countries there is a knowledge gap in the management of poisonings. We describe our experience with the worldwide delivery of an online introductory toxicology curriculum to emergency doctors and other health professionals treating poisoned patients. We delivered a 15-module introductory Internet-based toxicology curriculum to emergency doctors and health professionals, conducted from August to December 2016. This Internet-based curriculum was adapted from one used to teach emergency residents toxicology in the United States. Modules covered themes such as pharmaceutical (n = 8), toxidromes (n = 2) and agrochemicals (n = 5) poisoning. Participants completed pre-test and post-test multiple choice questions (MCQs) before and after completing the online module, respectively, throughout the course. We collected information on participant demographics, education and training, and perception of relevance of the curriculum. Participants gave feedback on the course and how it affected their practice. One hundred and thirty-six health professionals from 33 countries participated in the course: 98 emergency doctors/medical officers, 25 physicians, eight pharmacists/poisons information specialists, two toxicologists, two medical students and one nurse. Median age of participants was 34 years. Median number of years postgraduate was seven. Ninety (65%) had access to either a poisons information centre over the phone or toxicologist and 48 (35%) did not. All participants expected the course to help improve their knowledge. Overall median pre-module MCQ scores were 56% (95%CI: 38, 75%) compared to post-module MCQ scores median 89% (95% CI: 67, 100%) (p education to health professionals treating

Clinical, cytogenetic and toxicological studies in rural workers exposed to pesticides in Botucatu, São Paulo, Brazil

Directory of Open Access Journals (Sweden)

Salete Marcia Bréga

1998-01-01

Full Text Available Pesticides can cause gene mutations and chromosomal aberrations in exposed individuals. We have investigated 24 workers exposed to pesticides. Clinical examinations and cytogenetic and toxicological tests were performed. Ten non-exposed individuals were used as controls. Toxicological dosages of copper, zinc and manganese (metals found in some pesticides, hepatic enzyme dosage (GOT, GPT, AR and acetylcholinesterase activity were performed in 16 workers and 8 controls. In the exposed workers, the most relevant clinical symptoms were poor digestion with fullness sensation after meals, irritated eyes, headache and fasciculations. The exposed group showed significantly lower manganese dosage and acetylcholinesterase activity, and significantly higher levels of alkaline phosphatase. Cytogenetic studies showed significantly higher chromosomal aberrations in the exposed group compared to the control group. Although the workers used protection against the pesticide's fog, the results revealed that the workers were contaminated with the pesticides. Therefore, the cytogenetic, toxicological studies with clinical examination are necessary for monitoring workers who are exposed to pesticides in any situation.

Resource Guide to Careers in Toxicology, 3rd Edition.

Science.gov (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…

Environmental chemistry and toxicology of mercury

National Research Council Canada - National Science Library

Liu, Guangliang; Cai, Yong; O'Driscoll, Nelson J

2012-01-01

... employed in recent studies. The coverage discusses the environmental behavior and toxicological effects of mercury on organisms, including humans, and provides case studies at the end of each chapter...

A primer on systematic reviews in toxicology.

Science.gov (United States)

Hoffmann, Sebastian; de Vries, Rob B M; Stephens, Martin L; Beck, Nancy B; Dirven, Hubert A A M; Fowle, John R; Goodman, Julie E; Hartung, Thomas; Kimber, Ian; Lalu, Manoj M; Thayer, Kristina; Whaley, Paul; Wikoff, Daniele; Tsaioun, Katya

2017-07-01

Systematic reviews, pioneered in the clinical field, provide a transparent, methodologically rigorous and reproducible means of summarizing the available evidence on a precisely framed research question. Having matured to a well-established approach in many research fields, systematic reviews are receiving increasing attention as a potential tool for answering toxicological questions. In the larger framework of evidence-based toxicology, the advantages and obstacles of, as well as the approaches for, adapting and adopting systematic reviews to toxicology are still being explored. To provide the toxicology community with a starting point for conducting or understanding systematic reviews, we herein summarized available guidance documents from various fields of application. We have elaborated on the systematic review process by breaking it down into ten steps, starting with planning the project, framing the question, and writing and publishing the protocol, and concluding with interpretation and reporting. In addition, we have identified the specific methodological challenges of toxicological questions and have summarized how these can be addressed. Ultimately, this primer is intended to stimulate scientific discussions of the identified issues to fuel the development of toxicology-specific methodology and to encourage the application of systematic review methodology to toxicological issues.

OpenTox predictive toxicology framework: toxicological ontology and semantic media wiki-based OpenToxipedia.

Science.gov (United States)

Tcheremenskaia, Olga; Benigni, Romualdo; Nikolova, Ivelina; Jeliazkova, Nina; Escher, Sylvia E; Batke, Monika; Baier, Thomas; Poroikov, Vladimir; Lagunin, Alexey; Rautenberg, Micha; Hardy, Barry

2012-04-24

The OpenTox Framework, developed by the partners in the OpenTox project (http://www.opentox.org), aims at providing a unified access to toxicity data, predictive models and validation procedures. Interoperability of resources is achieved using a common information model, based on the OpenTox ontologies, describing predictive algorithms, models and toxicity data. As toxicological data may come from different, heterogeneous sources, a deployed ontology, unifying the terminology and the resources, is critical for the rational and reliable organization of the data, and its automatic processing. The following related ontologies have been developed for OpenTox: a) Toxicological ontology - listing the toxicological endpoints; b) Organs system and Effects ontology - addressing organs, targets/examinations and effects observed in in vivo studies; c) ToxML ontology - representing semi-automatic conversion of the ToxML schema; d) OpenTox ontology- representation of OpenTox framework components: chemical compounds, datasets, types of algorithms, models and validation web services; e) ToxLink-ToxCast assays ontology and f) OpenToxipedia community knowledge resource on toxicology terminology.OpenTox components are made available through standardized REST web services, where every compound, data set, and predictive method has a unique resolvable address (URI), used to retrieve its Resource Description Framework (RDF) representation, or to initiate the associated calculations and generate new RDF-based resources.The services support the integration of toxicity and chemical data from various sources, the generation and validation of computer models for toxic effects, seamless integration of new algorithms and scientifically sound validation routines and provide a flexible framework, which allows building arbitrary number of applications, tailored to solving different problems by end users (e.g. toxicologists). The OpenTox toxicological ontology projects may be accessed via the Open

Study of radiation protection at the Department of Radiology and Toxicology, Faculty of Health and Social Studies of University of South Bohemia

International Nuclear Information System (INIS)

Singer, J.; Kuna, P.

2005-01-01

In this paper authors deals with study of radiation protection at the Department of Radiology and Toxicology, Faculty of Health and Social Studies of University of South Bohemia. This department providing awareness of the concept of radiation protection in persons of different professions, who will come into contact with ionizing radiation sources. These are e.g. specialists in health services, employees in defectoscopy and industry, members of police and fire fighting services, etc. For these persons, the Department of Radiology and Toxicology was established at the Faculty of Health and Social Studies of University of South Bohemia that offer their relevant education in theory and practice of radiation problems that are accredited in following direction: bachelor study in Applied radiobiology and toxicology; bachelor study in Biophysics and medical techniques; and master study in Crisis radiobiology and toxicology. These specified subjects are arranged in such a way that the student can be introduced into the teaching text based on the concept and history of relevant problems, for example: radiation physics, ionizing radiation dosimetry, clinical dosimetry. In accordance with a survey implemented in the field of health services it was found that there is a lack of people with technical education in the field of radiation at the level of Bachelors. These requirements are most properly adhered to by the specialty 'Radiological Technician' that is currently being planned at the Faculty of Health and Social Studies and that will be subjected to the accreditation process. The specialty 'Radiological Assistant' was formerly accredited at the faculty, whose activity is different from that of the 'Radiological Technician', as defined by Law of the Czech Republic No. 96/2004 Sb

Ninth Triennial Toxicology Salary Survey.

Science.gov (United States)

Gad, Shayne Cox; Sullivan, Dexter Wayne

2016-01-01

This survey serves as the ninth in a series of toxicology salary surveys conducted at 3-year intervals and beginning in 1988. An electronic survey instrument was distributed to 5919 individuals including members of the Society of Toxicology, American College of Toxicology, and 23 additional professional organizations. Question items inquired about gender, age, degree, years of experience, certifications held, areas of specialization, society membership, employment and income. Overall, 1293 responses were received (response rate 21.8%). The results of the 2014 survey provide insight into the job market and career path for current and future toxicologists. © The Author(s) 2016.

Toxicological and performance aspects of oxygenated motor vehicle fuels

National Research Council Canada - National Science Library

National Research Council Staff; Commission on Life Sciences; Division on Earth and Life Studies; National Research Council; National Academy of Sciences

... COMMITTEE ON TOXICOLOGICAL PERFORMANCE ASPECTS OXYGENATED MOTOR VEHICLE FUELS ENVIRONMENTAL STUDIES TOXICOLOGY COMMISSION LIFE SCIENCES NATIONAL RESEARCH COUNCIL AND OF BOARD ON AND ON NATIONAL ACADEMY PRESS Washington, D.C. 1996 i Copyrightoriginal retained, the be not from cannot book, paper original however, for version formatting, authoritative the t...

A novel nasal powder formulation of glucagon: toxicology studies in animal models

OpenAIRE

Reno, Frederick E.; Normand, Patrick; McInally, Kevin; Silo, Sherwin; Stotland, Patricia; Triest, Myriam; Carballo, Dolores; Pich?, Claude

2015-01-01

Background Glucagon nasal powder (GNP), a novel intranasal formulation of glucagon being developed to treat insulin-induced severe hypoglycemia, contains synthetic glucagon (10?% w/w), beta-cyclodextrin, and dodecylphosphocholine. The safety of this formulation was evaluated in four studies in animal models. Methods The first study evaluated 28-day sub-chronic toxicology in rats treated intranasally with 1 and 2?mg of GNP/day (0.1 and 0.2?mg glucagon/rat/day). The second study evaluated 28-da...

The New Toxicology of Sophisticated Materials: Nanotoxicology and Beyond

Science.gov (United States)

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

2011-01-01

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

Prospects for applying synthetic biology to toxicology

DEFF Research Database (Denmark)

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

2017-01-01

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...

Developmental and Reproductive Toxicology Database (DART)

Data.gov (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...

On-line sources of toxicological information in Canada

International Nuclear Information System (INIS)

Racz, William J.; Ecobichon, Donald J.; Baril, Marc

2003-01-01

This paper will provide an overview of the on-line resources available in toxicology in Canada. It will describe a brief history of The Society of Toxicology of Canada, with reference to other societies and also provide information on education, research and other resources related to toxicology. Toxicology in Canada emerged as a distinct and vibrant discipline following the thalidomide tragedy of the 1960s. In the pharmaceutical industry and government, toxicology was readily established as an essential component of drug development and safety, and as the need for toxicologists expanded, training programs were established, usually in collaboration with departments of pharmacology. In the last two to three decades other disciplines, environmental biology, analytical chemistry and epidemiology joined the ranks of toxicology. The on-line sources of toxicology information are rapidly expanding. This article describes those sources considered by the authors to be important from a national and international perspective. The majority of these sources are professional organizations and government agencies

40 CFR 161.340 - Toxicology data requirements.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Toxicology data requirements. 161.340... Toxicology data requirements. (a) Table. Sections 161.100 through 161.102 describe how to use this table to determine the toxicology data requirements and the substance to be tested. Kind of data required (b) Notes...

Providing information regarding exposures in pregnancy: a survey of North American Teratology Information Services.

Science.gov (United States)

Hancock, Rebecca L; Ungar, Wendy J; Einarson, Adrienne; Goodstadt, Michael; Koren, Gideon

2008-04-01

Teratology Information Services (TIS) provide information on exposures during pregnancy and breast-feeding. Maintaining ongoing funding is a challenge. The purpose was to gather descriptive information on current TIS operations. All North American TIS (16 American, 2 Canadian) completed a detailed survey. Service goal ranked as most important was correction of risk misperceptions. Inquiries were primarily for medications (mean 43.5%, S.D. 14.1), lactation exposures, and workplace exposures. Median employees per TIS: three (range 1-12.5). Two TIS only counsel health care professionals (HCPs). Main callers to remaining TIS were pregnant women (mean 46.8%, S.D. 22.8), physicians, and nurses. Calls per week varied (median 20, range 4-600). Median annual budget: US dollars 69,000 (range dollars 3000-335,000). Seventeen TIS collect patient data for research. This survey was the first to document TIS operations in North America and demonstrates a spectrum of clinical and research activities, and provides data for a future cost-benefit analysis of TIS.

Data governance in predictive toxicology: A review.

Science.gov (United States)

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

2011-07-13

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

Data governance in predictive toxicology: A review

Directory of Open Access Journals (Sweden)

Fu Xin

2011-07-01

Full Text Available Abstract Background 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. 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. Conclusions 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

Current role of ICP-MS in clinical toxicology and forensic toxicology: a metallic profile.

Science.gov (United States)

Goullé, Jean-Pierre; Saussereau, Elodie; Mahieu, Loïc; Guerbet, Michel

2014-08-01

As metal/metalloid exposure is inevitable owing to its omnipresence, it may exert toxicity in humans. Recent advances in metal/metalloid analysis have been made moving from flame atomic absorption spectrometry and electrothermal atomic absorption spectrometry to the multi-elemental inductively coupled plasma (ICP) techniques as ICP atomic emission spectrometry and ICP-MS. ICP-MS has now emerged as a major technique in inorganic analytical chemistry owing to its flexibility, high sensitivity and good reproducibility. This in depth review explores the ICP-MS metallic profile in human toxicology. It is now routinely used and of great importance, in clinical toxicology and forensic toxicology to explore biological matrices, specifically whole blood, plasma, urine, hair, nail, biopsy samples and tissues.

History of the Journal of the American College of Toxicology.

Science.gov (United States)

Christian, Mildred S

2004-01-01

This companion article to the History of the American College of Toxicology also is written in celebration of the 25th Anniversary of the American College of Toxicology (ACT). It relates how the official journal of the College evolved from a privately owned publication, the Journal of Environmental Pathology and Toxicology (JEPT), into publications owned and managed by the College and its Board, for the first 17 years as the Journal of the American College of Toxicology (JACT) and currently as The International Journal of Toxicology (IJT). It relates how the first journal focused on toxicological studies, potential cancer causes and concerns associated with environmental contamination and chemical exposure safety issues. It tells how this journal was replaced by one more broadly based that addressed multiple industries and regulatory approaches, accepted previously unpublishable "no-effect" studies, so important in eliminating unwarranted animal use, and provided review articles, rather than only original research. It also described how the JACT evolved into an international journal finally recognized for its quality reviews and peer-reviewed research. Each of the three journals that represented the College is described, as well as interesting events associated with their development and publication, including the activities and contributions of the first four editors in chief, Drs. Myron A. Mehlman, Mildred S. Christian, Robert M. Diener and Harihara Mehendale.

The guinea pig as an animal model for developmental and reproductive toxicology studies.

Science.gov (United States)

Rocca, Meredith S; Wehner, Nancy G

2009-04-01

Regulatory guidelines for developmental and reproductive toxicology (DART) studies require selection of "relevant" animal models as determined by kinetic, pharmacological, and toxicological data. Traditionally, rats, mice, and rabbits are the preferred animal models for these studies. However, for test articles that are pharmacologically inactive in the traditional animal models, the guinea pig may be a viable option. This choice should not be made lightly, as guinea pigs have many disadvantages compared to the traditional species, including limited historical control data, variability in pregnancy rates, small and variable litter size, long gestation, relative maturity at birth, and difficulty in dosing and breeding. This report describes methods for using guinea pigs in DART studies and provides results of positive and negative controls. Standard study designs and animal husbandry methods were modified to allow mating on the postpartum estrus in fertility studies and were used for producing cohorts of pregnant females for developmental studies. A positive control study with the pregnancy-disrupting agent mifepristone resulted in the anticipated failure of embryo implantation and supported the use of the guinea pig model. Control data for reproductive endpoints collected from 5 studies are presented. In cases where the traditional animal models are not relevant, the guinea pig can be used successfully for DART studies. (c) 2009 Wiley-Liss, Inc.

Toxicodynetics: A new discipline in clinical toxicology.

Science.gov (United States)

Baud, F J; Houzé, P; Villa, A; Borron, S W; Carli, P

2016-05-01

Regarding the different disciplines that encompass the pharmacology and the toxicology, none is specifically dedicated to the description and analysis of the time-course of relevant toxic effects both in experimental and clinical studies. The lack of a discipline devoted to this major field in toxicology results in misconception and even in errors by clinicians. Review of the basic different disciplines that encompass pharmacology toxicology and comparing with the description of the time-course of effects in conditions in which toxicological analysis was not performed or with limited analytical evidence. Review of the literature clearly shows how misleading is the current extrapolation of toxicokinetic data to the description of the time-course of toxic effects. A new discipline entitled toxicodynetics should be developed aiming at a more systematic description of the time-course of effects in acute human and experimental poisonings. Toxicodynetics might help emergency physicians in risk assessment when facing a poisoning and contribute to a better assessment of quality control of data collected by poison control centres. Toxicodynetics would also allow a quantitative approach to the clinical effects resulting from drug-drug interaction. Copyright © 2016. Published by Elsevier Masson SAS.

Social housing of non-rodents during cardiovascular recordings in safety pharmacology and toxicology studies.

Science.gov (United States)

Prior, Helen; Bottomley, Anna; Champéroux, Pascal; Cordes, Jason; Delpy, Eric; Dybdal, Noel; Edmunds, Nick; Engwall, Mike; Foley, Mike; Hoffmann, Michael; Kaiser, Robert; Meecham, Ken; Milano, Stéphane; Milne, Aileen; Nelson, Rick; Roche, Brian; Valentin, Jean-Pierre; Ward, Gemma; Chapman, Kathryn

2016-01-01

The Safety Pharmacology Society (SPS) and National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs) conducted a survey and workshop in 2015 to define current industry practices relating to housing of non-rodents during telemetry recordings in safety pharmacology and toxicology studies. The aim was to share experiences, canvas opinion on the study procedures/designs that could be used and explore the barriers to social housing. Thirty-nine sites, either running studies (Sponsors or Contract Research Organisations, CROs) and/or outsourcing work responded to the survey (51% from Europe; 41% from USA). During safety pharmacology studies, 84, 67 and 100% of respondents socially house dogs, minipigs and non-human primates (NHPs) respectively on non-recording days. However, on recording days 20, 20 and 33% of respondents socially house the animals, respectively. The main barriers for social housing were limitations in the recording equipment used, study design and animal temperament/activity. During toxicology studies, 94, 100 and 100% of respondents socially house dogs, minipigs and NHPs respectively on non-recording days. However, on recording days 31, 25 and 50% of respondents socially house the animals, respectively. The main barriers for social housing were risk of damage to and limitations in the recording equipment used, food consumption recording and temperament/activity of the animals. Although the majority of the industry does not yet socially house animals during telemetry recordings in safety pharmacology and toxicology studies, there is support to implement this refinement. Continued discussions, sharing of best practice and data from companies already socially housing, combined with technology improvements and investments in infrastructure are required to maintain the forward momentum of this refinement across the industry. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Toxicological Studies of Mycotoxins Using Enzymatic and Histochemical Methods

Energy Technology Data Exchange (ETDEWEB)

Badea, Mihaela, E-mail: badeamihaela@yahoo.com; Taus, Nicoleta [Transilvania University of Brasov, Faculty of Medicine (Romania); Potrovita, Monica [Sanitary-Veterinary and Food Safety Direction of Brasov (Romania); Moarcas, Monica [Transilvania University of Brasov, Faculty of Medicine (Romania)

2009-08-15

Studies concerning mycotoxins involve activities of relevant potential for furthering knowledge in the fields of toxicology and environmental analysis. Using bioanalytical methods (biosensors, histochemistry), the conducted research aims at contributing to raising the awareness of local, national, and international media in relation to the safety of obtaining and processing vegetal and animal foods, by analyzing the possible effects of aflatoxins and ochratoxins, promoting animal health, food hygiene, in view of ensuring animal and human health. The study using laboratory animals (mice) while being part of one of the current national research directions, also holds international priority, by its contribution to a better understanding of several fundamental mechanisms of life at molecular level and to the characterization of certain biological processes that appear in mycotoxicosis.

Comparison of a modified mid-coronal sectioning technique and Wilson's technique when conducting eye and brain examinations in rabbit teratology studies.

Science.gov (United States)

Ziejewski, Mary K; Solomon, Howard M; Rendemonti, Joyce; Stanislaus, Dinesh

2015-02-01

There are two methods used when examining fetal rabbit eyes and brain in teratology studies. One method employs prior fixation before serial sectioning (Wilson's technique) and the other uses fresh tissue (mid-coronal sectioning). We modified the mid-coronal sectioning technique to include removal of eyes and brain for closer examination and to increase the number of structures that can be evaluated and compared it to the Wilson's technique. We found that external examination of the head, in conjunction with either sectioning method, is equally sensitive in identifying developmental defects. We evaluated 40,401 New Zealand White (NZW) and Dutch-Belted (DB) rabbit fetuses for external head alterations, of which 28,538 fetuses were further examined for eye and brain alterations using the modified mid-coronal sectioning method (16,675 fetuses) or Wilson's technique (11,863 fetuses). The fetuses were from vehicle control or drug-treated pregnant rabbits in embryo-fetal development studies conducted to meet international regulatory requirements for the development of new drugs. Both methods detected the more common alterations (microphthalmia and dilated lateral cerebral ventricles) and other less common findings (changes in size and/or shape of eye and brain structures). While both methods are equally sensitive at detecting common and rare developmental defects, the modified mid-coronal sectioning technique eliminates the use of chemicals and concomitant fixation artifacts that occur with the Wilson's technique and allows for examination of 100% intact fetuses thereby increasing potential for detecting eye and brain alterations as these findings occur infrequently in rabbits. © 2015 Wiley Periodicals, Inc.

The inhalation toxicology of p-aramid fibrils.

Science.gov (United States)

Donaldson, Ken

2009-01-01

The pandemic of lung disease caused by asbestos has cast suspicion on any industrial fibrous material that can become airborne in respirable form in workplaces, such that the respirable fibres might be inhaled. Fibre toxicology arose as a sub-specialty of particle toxicology to address the specialised nature of fibre effects and has evolved substantially in the last 25 years. It has yielded valuable information on the dosimetry, structure-activity relationships, and mechanism involved in toxicological effects of a range of fibrous materials, including asbestos, other naturally occurring fibrous materials, and synthetic vitreous fibres. A robust structure/activity paradigm has emerged from this research that highlights fibre length, thinness, and biopersistence as major factors in determining the pathogenicity of a fibre. p-Aramid is a manufactured fibre composed of synthetic polyamide (poly paraphenylene terephthalamide) manufactured on a commercial scale since 1970 by polymerisation and spinning steps. It is used as an advanced composite and in fabrics, body armour, friction materials, etc. Respirable fibrils of p-aramid can be released from the fibres during working and can become airborne. A considerable body of research has been carried out into the hazard posed by inhaled p-aramid fibrils, and this review considers this body of literature and summarises the state-of-the-science in the toxicology of p-aramid fibrils in the light of the existing overarching fibre toxicology paradigm. The peer-reviewed studies demonstrate that p-aramid fibrils can be long and thin but that the fibrils are not biopersistent. Residence in the milieu of the lungs leads to fibre shortening, allowing efficient and complete phagocytosis and effective clearance. Subsequently the p-aramid hazard is low, and this is confirmed in animal studies. The mechanism of shortening of p-aramid fibrils is not well-understood, but may involve the action of macrophages on the fibrils following

Toxicology of Biodiesel Combustion products

Science.gov (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. ...

Toxicological profile for thorium. Draft report (Final)

International Nuclear Information System (INIS)

1990-10-01

The ATSDR Toxicological Profile for Thorium is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substance's toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

Studies and activities in the field of chemical toxicology carried out by the service d'hygiene industrielle

International Nuclear Information System (INIS)

Chalabreysse, J.; Archimbaud, M.; Teulon, F.

1988-02-01

The Service d'Hygiene Industrielle (Industrial hygiene service, Institute of protection and nuclear safety, Department of health protection - IPSN-DPS) has acquired an unquestionable proficiency in chemical toxicology on account of 1) its missions of research on and monitoring of workers, working conditions and the environment on the Tricastin industrial complex and 2) of its actions of technical assistance to the CEA group and of valorization outside the group. The report presents how toxicological hazards originated from the use of chemical products by the nuclear industry are taken into consideration. A global methodology of assessment of chemical-toxicological hazards has been developed; it is based on the experience gained in various occupational branches (nuclear and non-nuclear industry, agriculture, administrations,...). The Service d'hygiene industrielle is developing R and D studies in the field of biology and analytical chemistry based on the present knowledge and doctrine in radiotoxicology (uranium especially). The contribution of radiation protection and radiotoxicology to non-nuclear industrial hygiene can thus be appreciated [fr

Toxicological perspectives of inhaled therapeutics and nanoparticles.

Science.gov (United States)

Hayes, Amanda J; Bakand, Shahnaz

2014-07-01

The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges. This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery. Traditionally, inhalation toxicity has been performed on test animals to identify the median lethal concentration of airborne materials. Later maximum tolerable concentration denoted by LC0 has been introduced as a more ethically acceptable end point. More recently, in vitro methods have been developed, allowing the direct exposure of airborne material to cultured human target cells on permeable porous membranes at the air-liquid interface. Modifications of current inhalation therapies, new pulmonary medications for respiratory diseases and implementation of the respiratory tract for systemic drug delivery are providing new challenges when conducting well-designed inhalation toxicology studies. In particular, the area of nanoparticles and nanocarriers is of critical toxicological concern. There is a need to develop toxicological test models, which characterise the toxic response and cellular interaction between inhaled particles and the respiratory system.

Developmental toxicology: adequacy of current methods.

Science.gov (United States)

Peters, P W

1998-01-01

Toxicology embraces several disciplines such as carcinogenicity, mutagenicity and reproductive toxicity. Reproductive toxicology is concerned with possible effects of substances on the reproductive process, i.e. on sexual organs and their functions, endocrine regulation, fertilization, transport of the fertilized ovum, implantation, and embryonic, fetal and postnatal development, until the end-differentiation of the organs is achieved. Reproductive toxicology is divided into areas related to male and female fertility, and developmental toxicology. Developmental toxicology can be further broken down into prenatal and postnatal toxicology. Today, much new information is available about the origins of developmental disorders resulting from chemical exposure. While these findings seem to promise important new developments in methodology and research, there is a danger of losing sight of the precepts and principles established in the light of existing knowledge. There is also a danger that we may fail to correct shortcomings in our existing procedures and practice. The aim of this presentation is to emphasize the importance of testing substances for their impact in advance of their use and to underline that we must use the best existing tools for carrying out risk assessments. Moreover, it needs to be stressed that there are many substances that are never assessed with respect to reproductive and developmental toxicity. Similarly, our programmes for post-marketing surveillance with respect to developmental toxicology are grossly inadequate. Our ability to identify risks to normal development and reproduction would be much improved, first if a number of straightforward precepts were always followed and second, if we had a clearer understanding of what we mean by risk and acceptable levels of risk in the context of development. Other aims of this paper are: to stress the complexity of the different stages of normal prenatal development; to note the principles that are

Toxicological aspects of water

International Nuclear Information System (INIS)

Garcia Puertas, P.

1991-01-01

Different toxicological aspects of water have been studied, remarking the activity of various chemical substances in the organism. These substances are divided in: trace metals (Sb, As, Cd, Zn, Cu, Cr, Fe, Mn, Hg, Ni, Pb, Se), other contaminants (CN-, polycyclic aromatic hydrocarbons, phenols, pesticides, detergents) and radioactivity. Finally, some considerations on this subject are made [es

Principles and procedures in forensic toxicology.

Science.gov (United States)

Wyman, John F

2012-09-01

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.

Toxicological effects and recovery of the corneal epithelium in Cyprinus carpio communis Linn. exposed to monocrotophos: an scanning electron microscope study.

Science.gov (United States)

Uppal, Ravneet Kaur; Johal, Mohinder Singh; Sharma, Madan Lal

2015-05-01

This study was conducted based on the evidence of fish habitats in North India being affected by organophosphate pesticides draining from agricultural fields into bodies of water, especially during the rainy season. Various tissues of fish such as scales, gills ovaries, kidney, and liver have been studied from the toxicological point of view, but the toxicological effects of aquatic pollutants on fish cornea have not been investigated to date. We conducted comparative toxicological studies on the cornea of Cyprinus carpio communis using two sublethal (0.038 and 0.126 ppm) concentrations of monocrotophos pesticide for 30 days. Corneas from all the groups were evaluated by a scanning electron microscope. The fish exposed to the monocrotophos pesticide developed corneal necrosis due to the formation of crystalloid-like structures, thinning and shrinkage of microridges on the corneal epithelium. After 30 days, fish from the monocrotophos-treated tank were transferred to normal environmental conditions. After 60 days under natural condition, epithelial cells did not fully recover. In conclusion, exposure to monocrotophos induces irreversible changes in the cornea of C. carpio communis. As fish and mammalian visual systems share many similarities, the reported finding may offer useful insights for further toxicological and ophthalmological studies in humans. © 2013 American College of Veterinary Ophthalmologists.

MicroRNAs and toxicology: A love marriage

Directory of Open Access Journals (Sweden)

Elisabeth Schraml

Full Text Available With the dawn of personalized medicine, secreted microRNAs (miRNAs have come into the very focus of biomarker development for various diseases. MiRNAs fulfil key requirements of diagnostic tools such as i non or minimally invasive accessibility, ii robust, standardized and non-expensive quantitative analysis, iii rapid turnaround of the test result and iv most importantly because they provide a comprehensive snapshot of the ongoing physiologic processes in cells and tissues that package and release miRNAs into cell-free space. These characteristics have also established circulating miRNAs as promising biomarker candidates for toxicological studies, where they are used as biomarkers of drug-, or chemical-induced tissue injury for safety assessment. The tissue-specificity and early release of circulating miRNAs upon tissue injury, when damage is still reversible, are main factors for their clinical utility in toxicology. Here we summarize in brief, current knowledge of this field. Keywords: microRNAs, Biomarker, Toxicology, Minimal-invasive, DILI

HEPATOPROTECTIVE AND TOXICOLOGICAL STUDIES ON MICROCEPHALA LAMELLATA, PERIPLOCA APHYLLA AND ALHAJI MOURARROUM

OpenAIRE

Rahiya Gul , Muhammad Youni, Shafi Muhammad*, Abdul Jabbar and Gul Dana

2018-01-01

Balochistan is native home of many medicinal plants. Peoples living in rural areas mostly rely on these medicinal plants to cure diseases. Microcephala lamellata, Periploca aphylla and Alhaji mourarroum are important medicinal plants used for cure of various diseases. Current study was carried to explore hepatoprotective and toxicological profile of these plants. Hepatoprotective activity was carried out by CCl4 induced liver damage in rabbits. Chronic toxicity test was carried out on rabbi...

Teratology study of amide derivatives of branched aliphatic carboxylic acids with 4-aminobenzensulfonamide in NMRI mice.

Science.gov (United States)

Onishi, Yuko; Okada, Akinobu; Noyori, Hiroko; Okamura, Ai; Hen, Naama; Yagen, Boris; Bialer, Meir; Fujiwara, Michio

2013-08-01

Valproic acid (VPA), widely used to treat epilepsy, bipolar disorders, and migraine prophylaxis, is known to cause neural tube and skeletal defects in humans and animals. Aminobenzensulfonamide derivatives of VPA with branched aliphatic carboxylic acids, namely 2-methyl-N-(4-sulfamoyl-phenyl)-pentanamide (MSP), 2-ethyl-N-(4-sulfamoyl-phenyl)-butyramide (ESB), 2-ethyl-4-methyl-N-(4-sulfamoyl-phenyl)-pentanamide (EMSP), and 2-ethyl-N-(4-sulfamoyl-benzyl)-butyramide (ESBB), have shown more potent anticonvulsant activity than VPA in preclinical testing. Here, we investigated the teratogenic effects of these analogous compounds of VPA in NMRI mice. Pregnant NMRI mice were given a single subcutaneous injection of either VPA at 1.8 or 3.6 mmol/kg, or MSP, ESB, EMSP, or ESBB at 1.8, 3.6, or 4.8 mmol/kg on gestation day (GD) 8. Cesarean section was performed on GD 18, and the live fetuses were examined for external and skeletal malformations. Compared with VPA, which induced neural tube defects (NTDs) in fetuses at 1.8 and 3.6 mmol/kg, the analog derivatives induced no NTDs at dose levels up to 4.8 mmol/kg (except for a single case of exencephaly at 4.8 mmol/kg MSP). Skeletal examination showed several abnormalities mainly at the axial skeletal level with VPA at 1.8 mmol/kg. Fused vertebrae and/or fused ribs were also observed with MSP, ESB, EMSP, and ESBB, they were less severe and seen at a lower incidence that those induced by VPA at the same dose level. In addition to exerting more potent preclinical antiepileptic activity, teratology comparison indicates that aminobenzensulfonamide analogs are generally more weakly teratogenic than VPA. © 2013 Wiley Periodicals, Inc.

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

Science.gov (United States)

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

2015-08-01

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.

Imaging mass spectrometry in drug development and toxicology.

Science.gov (United States)

Karlsson, Oskar; Hanrieder, Jörg

2017-06-01

During the last decades, imaging mass spectrometry has gained significant relevance in biomedical research. Recent advances in imaging mass spectrometry have paved the way for in situ studies on drug development, metabolism and toxicology. In contrast to whole-body autoradiography that images the localization of radiolabeled compounds, imaging mass spectrometry provides the possibility to simultaneously determine the discrete tissue distribution of the parent compound and its metabolites. In addition, imaging mass spectrometry features high molecular specificity and allows comprehensive, multiplexed detection and localization of hundreds of proteins, peptides and lipids directly in tissues. Toxicologists traditionally screen for adverse findings by histopathological examination. However, studies of the molecular and cellular processes underpinning toxicological and pathologic findings induced by candidate drugs or toxins are important to reach a mechanistic understanding and an effective risk assessment strategy. One of IMS strengths is the ability to directly overlay the molecular information from the mass spectrometric analysis with the tissue section and allow correlative comparisons of molecular and histologic information. Imaging mass spectrometry could therefore be a powerful tool for omics profiling of pharmacological/toxicological effects of drug candidates and toxicants in discrete tissue regions. The aim of the present review is to provide an overview of imaging mass spectrometry, with particular focus on MALDI imaging mass spectrometry, and its use in drug development and toxicology in general.

Toxicological aspects of energy production

International Nuclear Information System (INIS)

Sanders, C.L.

1986-01-01

Part I reviews the principles of toxicology, describes the biological fate of chemicals in the body, discusses basic pathobiology, and reviews short-term toxicity tests. Part II describes the toxicology and pathology of pollutants in several important organ systems. The greatest emphasis is placed on the respiratory tract because of its high probability as a route of exposure to pollutants from energy technologies and its high sensitivity to pollutant related tissue damage. Part III describes the toxicological aspects of specific chemical classes associated with fossil fuels; these include polycyclic hydrocarbons, gases and metals. Part IV describes the biomedical effects associated with each energy technology, including coal and oil, fossil fuel and biomass conversions, solar and geothermal and radiological health aspects associated with uranium mining, nuclear fission and fusion, and with nonionising radiations and electromagnetic fields

Shuttle Lesson Learned - Toxicology

Science.gov (United States)

James, John T.

2010-01-01

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.

Molecular dynamics simulations and applications in computational toxicology and nanotoxicology.

Science.gov (United States)

Selvaraj, Chandrabose; Sakkiah, Sugunadevi; Tong, Weida; Hong, Huixiao

2018-02-01

Nanotoxicology studies toxicity of nanomaterials and has been widely applied in biomedical researches to explore toxicity of various biological systems. Investigating biological systems through in vivo and in vitro methods is expensive and time taking. Therefore, computational toxicology, a multi-discipline field that utilizes computational power and algorithms to examine toxicology of biological systems, has gained attractions to scientists. Molecular dynamics (MD) simulations of biomolecules such as proteins and DNA are popular for understanding of interactions between biological systems and chemicals in computational toxicology. In this paper, we review MD simulation methods, protocol for running MD simulations and their applications in studies of toxicity and nanotechnology. We also briefly summarize some popular software tools for execution of MD simulations. Published by Elsevier Ltd.

[Research advances in eco-toxicological diagnosis of soil pollution].

Science.gov (United States)

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

2014-09-01

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.

Post-mortem toxicology in young sudden cardiac death victims

DEFF Research Database (Denmark)

Bjune, Thea; Risgaard, Bjarke; Kruckow, Line

2017-01-01

Aims: Several drugs increase the risk of ventricular fibrillation and sudden cardiac death (SCD). We aimed to investigate in detail the toxicological findings of all young SCD throughout Denmark. Methods and results: Deaths in persons aged 1-49 years were included over a 10-year period. Death...... 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...

Behavioral assays in environmental toxicology

Energy Technology Data Exchange (ETDEWEB)

Weiss, B.

1979-01-01

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.

Metabolomics in Toxicology and Preclinical Research

Science.gov (United States)

Ramirez, Tzutzuy; Daneshian, Mardas; Kamp, Hennicke; Bois, Frederic Y.; Clench, Malcolm R.; Coen, Muireann; Donley, Beth; Fischer, Steven M.; Ekman, Drew R.; Fabian, Eric; Guillou, Claude; Heuer, Joachim; Hogberg, Helena T.; Jungnickel, Harald; Keun, Hector C.; Krennrich, Gerhard; Krupp, Eckart; Luch, Andreas; Noor, Fozia; Peter, Erik; Riefke, Bjoern; Seymour, Mark; Skinner, Nigel; Smirnova, Lena; Verheij, Elwin; Wagner, Silvia; Hartung, Thomas; van Ravenzwaay, Bennard; Leist, Marcel

2013-01-01

Summary Metabolomics, the comprehensive analysis of metabolites in a biological system, provides detailed information about the biochemical/physiological status of a biological system, and about the changes caused by chemicals. Metabolomics analysis is used in many fields, ranging from the analysis of the physiological status of genetically modified organisms in safety science to the evaluation of human health conditions. In toxicology, metabolomics is the -omics discipline that is most closely related to classical knowledge of disturbed biochemical pathways. It allows rapid identification of the potential targets of a hazardous compound. It can give information on target organs and often can help to improve our understanding regarding the mode-of-action of a given compound. Such insights aid the discovery of biomarkers that either indicate pathophysiological conditions or help the monitoring of the efficacy of drug therapies. The first toxicological applications of metabolomics were for mechanistic research, but different ways to use the technology in a regulatory context are being explored. Ideally, further progress in that direction will position the metabolomics approach to address the challenges of toxicology of the 21st century. To address these issues, scientists from academia, industry, and regulatory bodies came together in a workshop to discuss the current status of applied metabolomics and its potential in the safety assessment of compounds. We report here on the conclusions of three working groups addressing questions regarding 1) metabolomics for in vitro studies 2) the appropriate use of metabolomics in systems toxicology, and 3) use of metabolomics in a regulatory context. PMID:23665807

Systems Toxicology: Real World Applications and Opportunities

Science.gov (United States)

2017-01-01

Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized from empirical end points to describing modes of action as adverse outcome pathways and perturbed networks. Toward this aim, Systems Toxicology entails the integration of in vitro and in vivo toxicity data with computational modeling. This evolving approach depends critically on data reliability and relevance, which in turn depends on the quality of experimental models and bioanalysis techniques used to generate toxicological data. Systems Toxicology involves the use of large-scale data streams (“big data”), such as those derived from omics measurements that require computational means for obtaining informative results. Thus, integrative analysis of multiple molecular measurements, particularly acquired by omics strategies, is a key approach in Systems Toxicology. In recent years, there have been significant advances centered on in vitro test systems and bioanalytical strategies, yet a frontier challenge concerns linking observed network perturbations to phenotypes, which will require understanding pathways and networks that give rise to adverse responses. This summary perspective from a 2016 Systems Toxicology meeting, an international conference held in the Alps of Switzerland, describes the limitations and opportunities of selected emerging applications in this rapidly advancing field. Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized, from empirical end points to pathways of toxicity. This requires the integration of in vitro and in vivo data with computational modeling. Test systems and bioanalytical technologies have made significant advances, but ensuring data reliability and relevance is an ongoing concern. The major challenge facing the new pathway approach is determining how to link observed network perturbations to phenotypic toxicity. PMID:28362102

Systems Toxicology: Real World Applications and Opportunities.

Science.gov (United States)

Hartung, Thomas; FitzGerald, Rex E; Jennings, Paul; Mirams, Gary R; Peitsch, Manuel C; Rostami-Hodjegan, Amin; Shah, Imran; Wilks, Martin F; Sturla, Shana J

2017-04-17

Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized from empirical end points to describing modes of action as adverse outcome pathways and perturbed networks. Toward this aim, Systems Toxicology entails the integration of in vitro and in vivo toxicity data with computational modeling. This evolving approach depends critically on data reliability and relevance, which in turn depends on the quality of experimental models and bioanalysis techniques used to generate toxicological data. Systems Toxicology involves the use of large-scale data streams ("big data"), such as those derived from omics measurements that require computational means for obtaining informative results. Thus, integrative analysis of multiple molecular measurements, particularly acquired by omics strategies, is a key approach in Systems Toxicology. In recent years, there have been significant advances centered on in vitro test systems and bioanalytical strategies, yet a frontier challenge concerns linking observed network perturbations to phenotypes, which will require understanding pathways and networks that give rise to adverse responses. This summary perspective from a 2016 Systems Toxicology meeting, an international conference held in the Alps of Switzerland, describes the limitations and opportunities of selected emerging applications in this rapidly advancing field. Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized, from empirical end points to pathways of toxicity. This requires the integration of in vitro and in vivo data with computational modeling. Test systems and bioanalytical technologies have made significant advances, but ensuring data reliability and relevance is an ongoing concern. The major challenge facing the new pathway approach is determining how to link observed network perturbations to phenotypic toxicity.

Implications of the stability behavior of zinc oxide nanoparticles for toxicological studies

Science.gov (United States)

Meißner, Tobias; Oelschlägel, Kathrin; Potthoff, Annegret

2014-08-01

The increasing use of zinc oxide (ZnO) nanoparticles in sunscreens and other cosmetic products demands a risk assessment that has to be done in toxicological studies. Such investigations require profound knowledge of the behavior of ZnO in cell culture media. The current study was performed to get well-dispersed suspensions of a hydrophilic (ZnO-hydro) and a lipophilic coated (ZnO-lipo) ZnO nanomaterial for use in in vitro tests. Therefore, systematic tests were carried out with common dispersants (phosphate, lecithin, proteins) to elucidate chemical and physical changes of ZnO nanoparticles in water and physiological solutions (PBS, DMEM). Non-physiological stock suspensions were prepared using ultrasonication. Time-dependent changes of pH, conductivity, zeta potential, particle size and dissolution were recorded. Secondly, the stock suspensions were added to physiological media with or without albumin (BSA) or serum (FBS), to examine characteristics such as agglomeration and dissolution. Stable stock suspensions were obtained using phosphate as natural and physiological electrostatic stabilizing agent. Lecithin proved to be an effective wetting agent for ZnO-lipo. Although the particle size remained constant, the suspension changed over time. The pH increased as a result of ZnO dissolution and formation of zinc phosphate complexes. The behavior of ZnO in physiological media was found to depend strongly on the additives used. Applying only phosphate as additive, ZnO-hydro agglomerated within minutes. In the presence of lecithin or BSA/serum, agglomeration was inhibited. ZnO dissolution was higher under physiological conditions than in the stock suspension. Serum especially promoted this process. Using body-related dispersants (phosphate, lecithin) non-agglomerating stock suspensions of hydrophilic and lipophilic ZnO were prepared as a prerequisite to perform meaningful toxicological investigation. Both nanomaterials showed a non-negligible dissolution behavior

42 CFR 493.845 - Standard; Toxicology.

Science.gov (United States)

2010-10-01

... 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 of...

Gordon Research Conference on Genetic Toxicology

Energy Technology Data Exchange (ETDEWEB)

Project Director Penelope Jeggo

2003-02-15

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

Juvenile Toxicology: Relevance and Challenges for Toxicologists and Pathologists

Science.gov (United States)

Remick, Amera K.; Catlin, Natasha R.; Quist, Erin M.; Steinbach, Thomas J.; Dixon, Darlene

2015-01-01

The Society of Toxicologic Pathology (STP) Education Committee and the STP Reproductive Special Interest Group held a North Carolina regional meeting entitled, “Juvenile Toxicology: Relevance and Challenges for Toxicologists and Pathologists” on March 13, 2015, at the National Institute of Environmental Health Sciences/National Toxicology Program in Research Triangle Park, North Carolina. The purpose of this regional meeting was to familiarize attendees with the topic of juvenile toxicity testing and discuss its relevance to clinical pediatric medicine, regulatory perspectives, challenges of appropriate study design confronted by toxicologists, and challenges of histopathologic examination and interpretation of juvenile tissues faced by pathologists. The 1-day meeting was a success with over 60 attendees representing industry, government, research organizations, and academia. PMID:26220944

Predictive toxicology: the paths of the future; Toxicologie predictive: les voies du futur

Energy Technology Data Exchange (ETDEWEB)

Detilleux, Ph.; Vallier, L.; Legallais, C.; Leclerc, E.; Prot, J.M.; Choucha, L.; Baudoin, R.; Dufresne, M.; Gautier, A.; Carpentier, B.; Mansuy, D.; Pery, A.; Brochot, C.; Manivet, Ph.; Rabilloud, Th.; Spire, C.; Coumoul, X.; Junot, Ch.; Laprevote, O.; Le pape, A.; Le Guevel, R.; Tourneur, E.; Ben Mkaddem, S.; Chassin, C.; Aloulou, M.; Goujon, J.M.; Hertif, A.; Ouali, N.; Vimont, S.; Monteiro, R.; Rondeau, E.; Elbim, C.; Werts, C.; Vandewalle, A.; Ben Mkaddem, S.; Pedruzzi, E.; Coant, N.; Bens, M.; Cluzeaud, F.; Ogier-Denis, E.; Pongnimitprasert, N.; Babin-Chevaye, C.; Fay, M.; Bernard, M.; Dupuy, C.; Ei Benna, J.; Gougerot-Pocidale, M.A.; Braut-Boucher, F.; Pinton, Ph.; Lucioli, J.; Tsybulskyy, D.; Joly, B.; Laffitte, J.; Bourges-Abella, N.; Oswald, I.P.; Kolf-Clauw, M.; Pierre, St.; Bats, A.S.; Chevallier, A.; Bui, L.Ch.; Ambolet-Camoit, A.; Garlatti, M.; Aggerbeck, M.; Barouki, R.; Al Khansa, I.; Blanck, O.; Guillouzo, A.; Bars, R.; Rouas, C.; Bensoussan, H.; Suhard, D.; Tessier, C.; Grandcolas, L.; Pallardy, M.; Gueguen, Y.; Sparfel, L.; Pinel-Marie, M.L.; Boize, M.; Koscielny, S.; Desmots, S.; Pery, A.; Fardel, O.; Alvergnas, M.; Rouleau, A.; Lucchi, G.; Mantion, G.; Heyd, B.; Richert, L.; Ducoroy, P.; Martin, H.; Val, St.; Martinon, L.; Cachier, H.; Yahyaoui, A.; Marfaing, H.; Baeza-Squiban, A.; Martin-Chouly, C.; Bonvallet, M.; Morzadec, C.; Fardel, O.; Vernhet, L.; Baverel, G.; El Hage, M.; Nazaret, R.; Conjard-Duplany, A.; Ferrier, B.; Martin, G.; Legendre, A.; Desmots, S.; Lecomte, A.; Froment, P.; Habert, R.; Lemazurier, E.; Robinel, F.; Dupont, O.; Sanfins, E.; Dairou, J.; Chaffotte, A.F.; Busi, F.; Rodrigues Lima, F.; Dupret, J.M.; Mayati, A.; Le Ferrec, E.; Levoin, N.; Paris, H.; Uriac, Ph.; N' Diaye, M.; Lagadic-Gossmann, D.; Fardel, O.; Assemat, E.; Boublil, L.; Borot, M.C.; Marano, F.; Baeza-Squiban, A.; Martiny, V.Y.; Moroy, G.; Badel, A.; Miteva, M.A.; Hussain, S.; Ferecatu, I.; Borot, C.; Andreau, K.; Baeza-Squiban, A. [and others

2010-07-01

Prevention of possible noxious effects in relation with the exposure to one or several chemical, physical or biological agents present in our domestic or professional environment is one of today's big public health stakes. Another stake is the better assessment of the risks linked with the use of health-care products. The efficacy and predictiveness of toxicology studies are directly related to the combination of alternate complementary methods and animal experiments (obtaining data from different species and with different models: in vitro, ex vivo and in vivo). Despite important efforts, the toxicological evaluation remains perfectible. The proceedings of this 2010 congress of the French Society of cell pharmaco-toxicology deal with recent advances, both scientific and technological, in 'predictive toxicology'. Four main topics are approached: cell and organ models, 'omics', in silico modeling, and new technologies (imaging, cell ships, high-speed processing). Among the different presentations, 3 abstracts present some recent advances in imaging techniques applied to toxicology studies. These are: 1 - first uses in toxicology of TOF-SIMS mass spectroscopy imaging (O. Laprevote, Paris-Descartes Univ. (FR)); 2 - Small animal imaging, a tool for predictive toxicology (A. Le Pape, CNRS Orleans (FR)); 3 - uranium localization at cell level using SIMS imaging technique (C. Rouas et al., IRSN Fontenay-aux-Roses (FR)). (J.S.)

2007 TOXICOLOGY AND RISK ASSESSMENT ...

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EPA has announced The 2007 Toxicology and Risk Assessment Conference Cincinnati Marriott North, West Chester (Cincinnati), OHApril 23- 26, 2007 - Click to register!The Annual Toxicology and Risk Assessment Conference is a unique meeting where several Government Agencies come together to discuss toxicology and risk assessment issues that are not only of concern to the government, but also to a broader audience including academia and industry. The theme of this year's conference is Emerging Issues and Challenges in Risk Assessment and the preliminary agenda includes: Plenary Sessions and prominent speakers (tentative) include: Issues of Emerging Chemical ContaminantsUncertainty and Variability in Risk Assessment Use of Mechanistic data in IARC evaluationsParallel Sessions:Uncertainty and Variability in Dose-Response Assessment Recent Advances in Toxicity and Risk Assessment of RDX The Use of Epidemiologic Data for Risk Assessment Applications Cumulative Health Risk Assessment:

Nails in Forensic Toxicology: An Update.

Science.gov (United States)

Solimini, Renata; Minutillo, Adele; Kyriakou, Chrystalla; Pichini, Simona; Pacifici, Roberta; Busardo, Francesco Paolo

2017-01-01

The analysis of nails as a keratinized matrix to detect drugs or illicit substances has been increasingly used in forensic and clinical toxicology as a complementary test, especially for the specific characteristics of stably accumulating substances for long periods of time. This allows a retrospective investigation of chronic drug abuse, monitoring continuous drug or pharmaceutical use, reveal in utero drug exposure or environmental exposures. We herein review the recent literature investigating drug incorporation mechanisms and drug detection in nails for forensic toxicological purposes. Mechanisms of drug incorporation have not yet been fully elucidated. However, some research has lately contributed to a better understanding of how substances are incorporated into nails, suggesting three potential mechanisms of drug incorporation: contamination from sweat, incorporation from nail bed and incorporation from germinal matrix. In addition, numerous methods dealing with the determination of drugs of abuse, medications and alcohol biomarkers in nails have been reported in studies over the years. The latter methods could find application in clinical and forensic toxicology. The studies herein reviewed point out how important it is to standardize and harmonize the methodologies (either pre-analytical or analytical) for nails analysis and the optimization of sampling as well as the development of proficiency testing programs and the determination of cut-off values. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Animal toxicology

Energy Technology Data Exchange (ETDEWEB)

Amdur, M.

1996-12-31

The chapter evaluates results of toxicological studies on experimental animals to investigate health effects of air pollutants and examines the animal data have predicted the response to human subject. Data are presented on the comparative toxicity of sulfur dioxide and sulfuric acid. The animal data obtained by measurement of airway resistance in guinea pigs and of bronchial clearance of particles in donkeys predicted clearly that sulfuric acid was more irritant than sulfur dioxide. Data obtained on human subjects confirmed this prediction. These acute studies also correctly predicted the comparative toxicity of the two compounds in two year studies of monkeys. Such chronic studies are not possible in human subjects but it is a reasonable to assume that sulfuric acid would be more toxic than sulfur dioxide. Current findings in epidemiological studies certainly support this assumption.

Manpower Development in Toxicology. EURO Reports and Studies, No. 9.

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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…

Current status and prospects of the toxicological assessment of engineered nanomaterials

International Nuclear Information System (INIS)

Pacchiarotti, Francesca; Grollino, Maria Giuseppa; Leter, Giorgio

2015-01-01

Nano toxicology is a branch of experimental toxicology dealing with identification and characterization of the harmful biological effects of engineered nanomaterials. The physico-chemical properties of these materials affect their biological level interactions. From the first generation of experimental studies it showed the need for adaptation to nanomaterials methodologies and toxicological evaluation of current strategies. Special challenges are presented by the variety of materials to be tested, from the definition of relevant dose quantities, by the standardization of the preparation and characterization of the nanomaterial in the biological sample matrices, by techniques for the determination of the biodistribution in the body. 'Omics' technologies are now an innovative tool for toxicological approach based on understanding the mechanisms of action, which will allow the most advanced laboratories to implement high-performance screening test. [it

Evaluation of a Hungarian acaricide original molecule based on its environmental toxicological studies.

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Szamosi, D; Oláh, B; Hirka, G; Pap, L; Gáty, S

2000-07-01

The results of the environmental toxicological investigations and their results of a new hungarian acaricide molecule (SZI-121) developed by the CHINOIN were summarized. The toxicological effects of the test item on different ecotoxicological test systems were investigated in the following tests: Bacterium, alga, and plant growth inhibition tests, acute immobilization and 21 days reproduction tests on Daphnia magna, acute fish test, closed bottle test, mobility, aerob degradation and adsorption/desorption tests on three different soils. No toxic effect was found in the bacterium, alga, plant growth inhibition and acute fish tests in the highest concentrations used. In the Daphnia immobilization test 0.14 mg/l LC50 value was established in the concentration range of 0.0128-40 mg/l applied. The test item showed similar characteristics as the reference item during the mobility test in soils, the adsorption/desorption study and the degradation investigations. In order to determine the environmental degradation rate further degradation investigations, as well as the nitrogen mineralization test and the model of concentration change in natural waters were performed.

IRIS Toxicological Review of Acrolein (2003 Final)

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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.

Zebrafish neurotransmitter systems as potential pharmacological and toxicological targets.

Science.gov (United States)

Rico, E P; Rosemberg, D B; Seibt, K J; Capiotti, K M; Da Silva, R S; Bonan, C D

2011-01-01

Recent advances in neurobiology have emphasized the study of brain structure and function and its association with numerous pathological and toxicological events. Neurotransmitters are substances that relay, amplify, and modulate electrical signals between neurons and other cells. Neurotransmitter signaling mediates rapid intercellular communication by interacting with cell surface receptors, activating second messenger systems and regulating the activity of ion channels. Changes in the functional balance of neurotransmitters have been implicated in the failure of central nervous system function. In addition, abnormalities in neurotransmitter production or functioning can be induced by several toxicological compounds, many of which are found in the environment. The zebrafish has been increasingly used as an animal model for biomedical research, primarily due to its genetic tractability and ease of maintenance. These features make this species a versatile tool for pre-clinical drug discovery and toxicological investigations. Here, we present a review regarding the role of different excitatory and inhibitory neurotransmitter systems in zebrafish, such as dopaminergic, serotoninergic, cholinergic, purinergic, histaminergic, nitrergic, glutamatergic, glycinergic, and GABAergic systems, and emphasizing their features as pharmacological and toxicological targets. The increase in the global knowledge of neurotransmitter systems in zebrafish and the elucidation of their pharmacological and toxicological aspects may lead to new strategies and appropriate research priorities to offer insights for biomedical and environmental research. Copyright © 2011 Elsevier Inc. All rights reserved.

Pilot-Reported Beta-Blockers Identified by Forensic Toxicology Analysis of Postmortem Specimens.

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Canfield, Dennis V; Dubowski, Kurt M; Whinnery, James M; Forster, Estrella M

2018-01-01

This study compared beta-blockers reported by pilots with the medications found by postmortem toxicology analysis of specimens received from fatal aviation accidents between 1999 and 2015. Several studies have compared drugs using the standard approach: Compare the drug found by toxicology analysis with the drug reported by the pilot. This study uniquely examined first the pilot-reported medication and then compared it to that detected by toxicology analysis. This study will serve two purposes: (i) to determine the capability of a toxicology laboratory to detect reported medications, and (ii) to identify pilots with medications below detectable limits. All information required for this study was extracted from the Toxicology Data Base system and was searched using ToxFlo or SQL Server Management Studio. The following information was collected and analyzed: pilot-reported trade and/or generic drug, date specimens received, time of accident, type of aviation operations (CFR), state, pilot level, age, class of medical, specimen type, specimen concentration, dose reported, frequency reported associated with the accident, quantity reported, National Transportation Safety Board (NTSB) accident event number, and all NTSB reports. There were 319 pilots that either reported taking a beta-blocker or were found to be taking a beta-blocker by postmortem toxicology analysis. Time of death, therapeutic concentration and specimen type were found to be factors in the ability of the laboratory to detect beta-blockers. Beta-blockers taken by pilots will, in most cases, be found by a competent postmortem forensic toxicology laboratory at therapeutic concentrations. The dose taken by the pilot was not found to be a factor in the ability of the laboratory to identify beta-blockers. Time of dose, route of administration, specimen tested and therapeutic concentration of the drug were found to be factors in the ability of the laboratory to identify beta-blockers in postmortem specimens

In vivo acute toxicological studies of an antioxidant extract from Mangifera indica L. (Vimang).

Science.gov (United States)

Garrido, Gabino; Rodeiro, Idania; Hernández, Ivones; García, Gastón; Pérez, Gema; Merino, Nelson; Núñez-Sellés, Alberto; Delgado, René

2009-01-01

Mango (Mangifera indica L.) stem bark aqueous extract (MSBE) is a natural product with antioxidant, anti-inflammatory, analgesic, and immunomodulatory effects. Its formulations (e.g., tablets, capsules, syrup, vaginal oval, and suppositories) are known by the brand name of Vimang. In view of the ethnomedical, preclinical, and clinical uses of this extract and the necessity to assess its possible toxicological effect on man, a toxicological analysis of a standard extract is reported in this paper. Acute toxicity was evaluated in mice and rats by oral, dermal, and intraperitoneal (i.p.) administration. The extract, by oral or dermal administration, showed no lethality at the limit doses of 2,000 mg/kg body weight and no adverse effects were found. Deaths occurred with the i.p. administration at 200, but not 20 mg/kg in mice. MSBE was also studied on irritant tests in rabbits, and the results showed that it was nonirritating on skin, ocular, or rectal mucosa. The extract had minimal irritancy following vaginal application.

Ethnobotanical, phytochemical and toxicological studies of Xanthium strumarium L.

Science.gov (United States)

Islam, Mohammad Rashedul; Uddin, Mohammad Zashim; Rahman, Mohammad Sharifur; Tutul, Ershad; Rahman, Mohammed Zakiur; Hassan, Md Abul; Faiz, M A; Hossain, Moazzem; Hussain, Maleeha; Rashid, Mohammad Abdur

2009-12-01

The present study describes the ethnobotanical, phytochemical, and toxicological evaluations of Xanthium strumarium L. growing in Bangladesh. In toxicity evaluation on rats, the methanol extract of seedlings showed mortality, while both seedling and mature plant extracts raised the serum alanine transaminase and aspartate transaminase values and produced significant abnormalities in the histopathology of liver and kidney of rats. On the other hand, the aqueous soluble fraction of methanol extract of mature plant (LC50 = 0.352 microg/mL) and methanol crude extract of seedlings (LC50 = 0.656 microg/mL) demonstrated significant toxicity in the brine shrimp lethality bioassay. A total of four compounds were purified and characterized as stigmasterol (1), 11-hydroxy-11-carboxy-4-oxo-1(5),2(Z)-xanthadien-12,8-olide (2), daucosterol (3) and lasidiol-10-anisate (4). The present study suggests that X. strumarium is toxic to animal.

75 FR 64311 - National Toxicology Program (NTP); Office of Liaison, Policy and Review Meeting of the NTP Board...

Science.gov (United States)

2010-10-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP); Office of Liaison... preliminary study recommendations (see ``Request for Comments'' below). The NTP welcomes toxicology study... in toxicology that could be appropriately addressed through studies on the nominated substance(s...

Toxicology profiles of chemical and radiological contaminants at Hanford

International Nuclear Information System (INIS)

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

1995-07-01

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

Toxicology profiles of chemical and radiological contaminants at Hanford

Energy Technology Data Exchange (ETDEWEB)

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

1995-07-01

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

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

1998-12-31

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.)

Collection of biological samples in forensic toxicology.

Science.gov (United States)

Dinis-Oliveira, R J; Carvalho, F; Duarte, J A; Remião, F; Marques, A; Santos, A; Magalhães, T

2010-09-01

Forensic toxicology is the study and practice of the application of toxicology to the purposes of the law. The relevance of any finding is determined, in the first instance, by the nature and integrity of the specimen(s) submitted for analysis. This means that there are several specific challenges to select and collect specimens for ante-mortem and post-mortem toxicology investigation. Post-mortem specimens may be numerous and can endow some special difficulties compared to clinical specimens, namely those resulting from autolytic and putrefactive changes. Storage stability is also an important issue to be considered during the pre-analytic phase, since its consideration should facilitate the assessment of sample quality and the analytical result obtained from that sample. The knowledge on degradation mechanisms and methods to increase storage stability may enable the forensic toxicologist to circumvent possible difficulties. Therefore, advantages and limitations of specimen preservation procedures are thoroughfully discussed in this review. Presently, harmonized protocols for sampling in suspected intoxications would have obvious utility. In the present article an overview is given on sampling procedures for routinely collected specimens as well as on alternative specimens that may provide additional information on the route and timing of exposure to a specific xenobiotic. Last, but not least, a discussion on possible bias that can influence the interpretation of toxicological results is provided. This comprehensive review article is intented as a significant help for forensic toxicologists to accomplish their frequently overwhelming mission.

Advancing alternatives analysis: The role of predictive toxicology in selecting safer chemical products and processes.

Science.gov (United States)

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

2017-09-01

Alternatives analysis (AA) is a method used in regulation and product design to identify, assess, and evaluate the safety and viability of potential substitutes for hazardous chemicals. It requires toxicological data for the existing chemical and potential alternatives. Predictive toxicology uses in silico and in vitro approaches, computational models, and other tools to expedite toxicological data generation in a more cost-effective manner than traditional approaches. The present article briefly reviews the challenges associated with using predictive toxicology in regulatory AA, then presents 4 recommendations for its advancement. It recommends using case studies to advance the integration of predictive toxicology into AA, adopting a stepwise process to employing predictive toxicology in AA beginning with prioritization of chemicals of concern, leveraging existing resources to advance the integration of predictive toxicology into the practice of AA, and supporting transdisciplinary efforts. The further incorporation of predictive toxicology into AA would advance the ability of companies and regulators to select alternatives to harmful ingredients, and potentially increase the use of predictive toxicology in regulation more broadly. Integr Environ Assess Manag 2017;13:915-925. © 2017 SETAC. © 2017 SETAC.

Inhalation Toxicology Research Institute. Annual report, October 1, 1978-September 30, 1979

International Nuclear Information System (INIS)

Henderson, R.F.; Diel, J.H.; Martinez, B.S.

1979-12-01

Research information is given by the annual report from the Inhalation Toxicology Research Institute with abstracts for each of the 109 papers. Major sections of interest are nuclear energy toxicology, solar energy toxicology, diesel technology toxicology, coal technology toxicology, and conservation technology toxicology. Also included are seven appendices covering publications of technical reports and publications in open literature, abstracts publications in the open literature, seminars presented by visiting scientists and presentations before scientific meetings, organization of the Inhalation Toxicology Research Institute, and the status of experiments using beagle dogs

Applications of radiotracer techniques for the toxicology studies of nanomaterials

International Nuclear Information System (INIS)

Ma Yuhui; Zhang Zhiyong; Zhang Yuan; He Xiao; Zhang Haifeng; Chai Zhifang

2008-01-01

With the rapid development of nanosciences and nanotechnology, a wide variety of manufactured nanomaterials are now used in commodities, pharmaceutics, cosmetics, biomedical products, and industries. While nanomaterials possess more novel and unique physicochemical properties than bulk materials, they also have an unpredictable impact on human health. In the toxicology studies of nanomaterials, it is essential to know the basic behaviors in vivo, that is absorption, distribution, metabolism, and excretion (ADME) of these newly designed materials. Radiotracer techniques are especially well suited to such studies and has got the chance to demonstrate its enchantment. In this presentation, studies on radiotracer techniques used in nanotoxicology will be reviewed and new progresses at Institute of High Energy Physics, including the label methods and behaviors of labeled nanomaterials, such as fullerene, carbon nanotubes, and nanometer metal oxide in animals and in aquatic environments will be reported. (authors)

75 FR 21003 - National Toxicology Program (NTP); Office of Liaison, Policy and Review Meeting of the NTP Board...

Science.gov (United States)

2010-04-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP); Office of Liaison... toxicology study information from completed, ongoing, or anticipated studies, as well as information on... issues or topics in toxicology that could be appropriately addressed through studies on the nominated...

Veterinary Forensic Toxicology.

Science.gov (United States)

Gwaltney-Brant, S M

2016-09-01

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.

Systems Toxicology: From Basic Research to Risk Assessment

Science.gov (United States)

2014-01-01

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. PMID:24446777

La toxicología en la Universidad de Sevilla

OpenAIRE

Puerto Rodríguez, María; Cameán Fernández, Ana María; Moreno Navarro, Isabel María; Pichardo Sánchez, Silvia; Prieto Ortega, Ana Isabel; Jos Gallego, Ángeles Mencía

2010-01-01

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 ...

Space Toxicology: Human Health during Space Operations

Science.gov (United States)

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

2010-01-01

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.

[Forensic medicine as the cradle of toxicology in Russia].

Science.gov (United States)

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

2013-01-01

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.

Ovarian toxicity and carcinogenicity in eight recent national toxicology program studies

Energy Technology Data Exchange (ETDEWEB)

Maronpot, R.R.

1987-08-01

Ovarian toxicity and/or carcinogenicity has been documented for at least eight chemicals recently tested in National Toxicity Program prechronic and chronic rodent studies. The chemicals that yielded treatment-related ovarian lesions were 1,3-butadiene, 4-vinylcyclohexene, vinylcylohexene deipoxide, nitrofurantoin, nitrofurazone, benzene, ..delta..-9-tetrahydrocannabinol, and tricresylphosphate. Typical nonneoplastic ovarian changes included hypoplasia, atrophy, follicular necrosis, and tubular hyperplasia. The most commonly observed treatment-related neoplasms were granulosa cell tumors and benign mixed tumors. A relationship between antecedent ovarian hypoplasia, atrophy, and hyperplasia and subsequent ovarian neoplasia is supported by some of these National Toxicology Program studies. Pathologic changes in other tissues such as the adrenal glands and uterus were associated with the treatment-related ovarian changes.

SERS as a tool for in vitro toxicology.

Science.gov (United States)

Fisher, Kate M; McLeish, Jennifer A; Jamieson, Lauren E; Jiang, Jing; Hopgood, James R; McLaughlin, Stephen; Donaldson, Ken; Campbell, Colin J

2016-06-23

Measuring markers of stress such as pH and redox potential are important when studying toxicology in in vitro models because they are markers of oxidative stress, apoptosis and viability. While surface enhanced Raman spectroscopy is ideally suited to the measurement of redox potential and pH in live cells, the time-intensive nature and perceived difficulty in signal analysis and interpretation can be a barrier to its broad uptake by the biological community. In this paper we detail the development of signal processing and analysis algorithms that allow SERS spectra to be automatically processed so that the output of the processing is a pH or redox potential value. By automating signal processing we were able to carry out a comparative evaluation of the toxicology of silver and zinc oxide nanoparticles and correlate our findings with qPCR analysis. The combination of these two analytical techniques sheds light on the differences in toxicology between these two materials from the perspective of oxidative stress.

Analysis of volatile combustion products and a study of their toxicological effects.

Science.gov (United States)

Seader, J. D.; Einhorn, I. N.; Drake, W. O.; Mihlfeith, C. M.

1972-01-01

An experimental program was conducted to study the thermochemical, flammability and toxicological characteristics of uncoated and coated polyisocyanurate foams. The coatings used were fluorinated copolymer and an intumescent material. Combustion and pyrolysis gases were analyzed by gas chromatography and mass spectrometry. The LD-50 and LD-100 tests were performed on Sprague-Dawley rats housed in an environmental chamber. The isocyanurate foam, fluorinated-copolymer-coated foam, and the intumescent-coated foam were found to have excellent flammability and insulation characteristics, although smoke development was substantial.

Integrating Personalized Technology in Toxicology: Sensors, Smart Glass, and Social Media Applications in Toxicology Research.

Science.gov (United States)

Carreiro, Stephanie; Chai, Peter R; Carey, Jennifer; Chapman, Brittany; Boyer, Edward W

2017-06-01

Rapid proliferation of mobile technologies in social and healthcare spaces create an opportunity for advancement in research and clinical practice. The application of mobile, personalized technology in healthcare, referred to as mHealth, has not yet become routine in toxicology. However, key features of our practice environment, such as frequent need for remote evaluation, unreliable historical data from patients, and sensitive subject matter, make mHealth tools appealing solutions in comparison to traditional methods that collect retrospective or indirect data. This manuscript describes the features, uses, and costs associated with several of common sectors of mHealth research including wearable biosensors, ingestible biosensors, head-mounted devices, and social media applications. The benefits and novel challenges associated with the study and use of these applications are then discussed. Finally, opportunities for further research and integration are explored with a particular focus on toxicology-based applications.

Sperm characteristics and teratology in rats following vas deferens occlusion with RISUG and its reversal.

Science.gov (United States)

Lohiya, N K; Suthar, R; Khandelwal, A; Goyal, S; Ansari, A S; Manivannan, B

2010-02-01

The functional success of the reversal of vas occlusion by styrene maleic anhydride (RISUG), using the solvent vehicle, Dimethyl Sulphoxide (DMSO), has been investigated. Reversal with DMSO was carried out in Wistar albino rats 90 days after bilateral vas occlusion. The body weight, organ weight, sperm characteristics, fertility test and teratology, including skeletal morphology were evaluated in vas occlusion and reversal animals and in F(1) progenies to assess the functional success of the occlusion and reversal. Body weight, organ weight and the cauda epididymal sperm characteristics of vas occlusion and reversal animals and of F(1) progenies were comparable to control. Ejaculated spermatozoa in the vaginal smear showed detached head/tail, acrosomal damage, bent midpiece, bent tail and morphological aberrations in sperm head after vas occlusion, which returned to normal, 90 days after reversal. Monthly fertility test, post-injection showed 0% fertility, which improved gradually and 100% fertility was achieved 90 days after reversal. The fertility/pregnancy/implantation record and skeletal morphology of the offspring were comparable to control. The results suggest functional success and safety of vas occlusion reversal by DMSO.

Overview of Forensic Toxicology, Yesterday, Today and in the Future.

Science.gov (United States)

Chung, Heesun; Choe, Sanggil

2017-01-01

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 benchtop 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 epub@benthamscience.org.

Developmental biology and the study of malformations.

Science.gov (United States)

Hughes, A F

1976-05-01

Experimental work on abnormal conditions of incubation in the chick has been undertaken to acquire a scientific approach to malformations. More precise experiments on causing abnormalities had a common origin with experimental embryology. Progress in experimental teratology during the last 50 years is reviewed in a commentary on the 4 principles formulated by Stockard in 1921. The results of cytogenetical studies in man and in other organisms have led to the tracing of some relationships between them. Present knowledge concerning malformations of the neural tube, originating either experimentally, spontaneously, or phenotypically, has been presented and the teratological implications of some recent theories on the expression of the genotype are discussed in particular reference to problems of hormones as teratogens, the implication of carbohydrate metabolism, and teratogenesis. It is speculated that teratogenesis is possibly related to cationic balance in early development and that 1 factor retarding progress in the understanding of malformations is the tendency toward the development of teratology in an adequately close relationship with other branches of cell biology.

Forensic toxicology in drug-facilitated sexual assault.

Science.gov (United States)

Dinis-Oliveira, Ricardo Jorge; Magalhães, Teresa

2013-09-01

The low rates of reporting, prosecution and conviction that characterize sexual assault, is likely even more evident in drug-facilitated cases. Typically, in these crimes, victims are incapacitated and left unable to resist sexual advances, unconscious, unable to fight off the abuser or to say "no" and unable to clearly remember the circumstances surrounding the events due to anterograde amnesia. The consequence is the delay in performing toxicological analysis aggravated by the reluctance of the victim to disclose the crime. Moreover since "date rape drugs" are often consumed with ethanol and exhibit similar toxicodynamic effects, the diagnosis is erroneously performed as being classical ethanol intoxication. Therefore, it is imperative to rapidly consider toxicological analysis in drug-facilitated sexual assaults. The major focus of this review is to harmonize practical approaches and guidelines to rapidly uncover drug-facilitated sexual assault, namely issues related to when to perform toxicological analysis, toxicological requests, samples to be collected, storage, preservation and transport precautions and xenobiotics or endobiotics to be analyzed.

Toxicologic Laboratory Findings in Cases Reported with Hanging Death: a Two-Year Retrospective Study in Northeast Iran

Directory of Open Access Journals (Sweden)

Mohammad Ranjbar

2013-09-01

How to cite this article: Ranjbar R, Liaghat AR, Ranjbar A, Mohabbati H. Toxicologic Laboratory Findings in Cases Reported with Hanging Death: a Two-Year Retrospective Study in Northeast Iran. Asia Pac J Med Toxicol 2013;2:92-5.

The study of forensic toxicology should not be neglected in Japanese universities.

Science.gov (United States)

Ishihara, Kenji; Yajima, Daisuke; Abe, Hiroko; Nagasawa, Sayaka; Nara, Akina; Iwase, Hirotaro

2015-04-01

Forensic toxicology is aimed at identifying the relationship between drugs or poison and the cause of death or crime. In the authors' toxicology laboratory at Chiba University, the authors analyze almost every body for drugs and poisons. A simple inspection kit was used in an attempt to ascertain drug abuse. A mass spectrometer is used to perform highly accurate screening. When a poison is detected, quantitative analyses are required. A recent topic of interest is new psychoactive substances (NPS). Although NPS-related deaths may be decreasing, use of NPS as a cause of death is difficult to ascertain. Forensic institutes have recently begun to perform drug and poison tests on corpses. However, this approach presents several problems, as are discussed here. The hope is that highly accurate analyses of drugs and poisons will be performed throughout the country.

ACToR - Aggregated Computational Toxicology Resource

International Nuclear Information System (INIS)

Judson, Richard; Richard, Ann; Dix, David; Houck, Keith; Elloumi, Fathi; Martin, Matthew; Cathey, Tommy; Transue, Thomas R.; Spencer, Richard; Wolf, Maritja

2008-01-01

ACToR (Aggregated Computational Toxicology Resource) is a database and set of software applications that bring into one central location many types and sources of data on environmental chemicals. Currently, the ACToR chemical database contains information on chemical structure, in vitro bioassays and in vivo toxicology assays derived from more than 150 sources including the U.S. Environmental Protection Agency (EPA), Centers for Disease Control (CDC), U.S. Food and Drug Administration (FDA), National Institutes of Health (NIH), state agencies, corresponding government agencies in Canada, Europe and Japan, universities, the World Health Organization (WHO) and non-governmental organizations (NGOs). At the EPA National Center for Computational Toxicology, ACToR helps manage large data sets being used in a high-throughput environmental chemical screening and prioritization program called ToxCast TM

Coastal marine pollution and toxicology : overview of current research and future needs

International Nuclear Information System (INIS)

Zubir Din

1996-01-01

The contents are marine pollution and toxicology studies at Universiti Sains Malaysia, their facilities, and research projects have been done on this subject. In coastal pollution monitoring and baseline studies, the emphasis have been on determination of levels of trace-metals in the coastal marine environment, in relation to other physico-chemical parameters. The future needs and goals of marine pollution and toxicology studies in Malaysia also discussed

Coastal marine pollution and toxicology : overview of current research and future needs

Energy Technology Data Exchange (ETDEWEB)

Din, Zubir [Science Univ. of Malaysia, Minden, Pulau Pinang (Malaysia). Centre for Marine and Coastal Studies

1997-12-31

The contents are marine pollution and toxicology studies at Universiti Sains Malaysia, their facilities, and research projects have been done on this subject. In coastal pollution monitoring and baseline studies, the emphasis have been on determination of levels of trace-metals in the coastal marine environment, in relation to other physico-chemical parameters. The future needs and goals of marine pollution and toxicology studies in Malaysia also discussed.

Managing fertile women under lithium treatment: the challenge of a Teratology Information Service.

Science.gov (United States)

Neri, Caterina; De Luca, Carmen; D'oria, Luisa; Licameli, Angelo; Nucci, Marta; Pellegrino, Marcella; Caruso, Alessandro; De Santis, Marco

2018-06-01

The objective of the present study is to review the literature regarding the management of fertile patients under lithium treatment for bipolar disorder and to report the experience of our Teratology Information Service over the past thirteen years in managing women treated with lithium during preconception, pregnancy and breastfeeding. This research focuses on a selective review of the literature and a retrospective survey has been carried out on fertile women under lithium treatment who called our service at A. Gemelli University Hospital in Rome from May 2002 to December 2015. A total of 140 women under lithium treatment called our TIS. A complete follow-up has been performed on 34 patients: 29 called during pregnancy and 5 called during preconception. None of the patients called during breastfeeding, while half of the patients were taking concomitant drugs during pregnancy. One major cardiac malformation (hypoplastic left heart syndrome) has been reported. No minor malformations have been detected. Twenty-one patients delivered a living child, with one premature neonate. Two patients underwent voluntary interruption of pregnancy and six patients had early spontaneous abortion. In one patient, intrauterine growth retardation occurred, but with no adverse neonatal outcomes. Four neonates experienced transient respiratory distress at birth. Two children developed mild to severe language delay, but normal motor development. Lithium treatment in fertile women is a very delicate topic, where risks and benefits of discontinuing therapy when women plan to become pregnant should be accurately evaluated. Thorough peri-conceptional counselling is crucial for the outcome of pregnancy and for maternal health status during preconception, gestation and breastfeeding.

Drug screening in clinical or forensic toxicology: are there differences?

Science.gov (United States)

Gerostamoulos, Dimitri; Beyer, Jochen

2010-09-01

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.

Reproductive and developmental toxicology

National Research Council Canada - National Science Library

Gupta, Ramesh C

2011-01-01

.... 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...

Evidence-based toxicology for the 21st century: opportunities and challenges.

Science.gov (United States)

Stephens, Martin L; Andersen, Melvin; Becker, Richard A; Betts, Kellyn; Boekelheide, Kim; Carney, Ed; Chapin, Robert; Devlin, Dennis; Fitzpatrick, Suzanne; Fowle, John R; Harlow, Patricia; Hartung, Thomas; Hoffmann, Sebastian; Holsapple, Michael; Jacobs, Abigail; Judson, Richard; Naidenko, Olga; Pastoor, Tim; Patlewicz, Grace; Rowan, Andrew; Scherer, Roberta; Shaikh, Rashid; Simon, Ted; Wolf, Douglas; Zurlo, Joanne

2013-01-01

The Evidence-based Toxicology Collaboration (EBTC) was established recently to translate evidence-based approaches from medicine and health care to toxicology in an organized and sustained effort. The EBTC held a workshop on "Evidence-based Toxicology for the 21st Century: Opportunities and Challenges" in Research Triangle Park, North Carolina, USA on January 24-25, 2012. The presentations largely reflected two EBTC priorities: to apply evidence-based methods to assessing the performance of emerging pathway-based testing methods consistent with the 2007 National Research Council report on "Toxicity Testing in the 21st Century" as well as to adopt a governance structure and work processes to move that effort forward. The workshop served to clarify evidence-based approaches and to provide food for thought on substantive and administrative activities for the EBTC. Priority activities include conducting pilot studies to demonstrate the value of evidence-based approaches to toxicology, as well as conducting educational outreach on these approaches.

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

Science.gov (United States)

Kabata, Piotr Maciej; Waldman, Wojciech; Sein Anand, Jacek

2015-01-01

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. 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. 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. 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. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

STUDY OF INTERACTION BETWEEN LEAD AND GASTRIC MUCOSAL PROTEIN OF RATS WITH FORENSIC TOXICOLOGY APPROACH

Directory of Open Access Journals (Sweden)

Iwan Aflanie

2017-09-01

Full Text Available Abstract: Recently, forensic toxicology has been an interesting concern, especially in exposing the phenomena associated with the law. Using the forensic toxicology approach, several cases of lead (Pb poisoning have been widely revealed. In this present study will be investigate the interaction between Pb and amino acid gastric mucosal constituent proteins, especially cysteine and tyrosine groups. This research is a pure experimental research with posttest control group design, which is divided into 4 groups with 6 rats (Rattus novergicus in each group. Treatment in each group as follows; P0 was control group were given 2 ml of distilled water; P1 = administration of Pb 0.1 g/L; P2 = Pb administration of 1 mg/L; and P3 = Pb administration of 10 g/L for 4 weeks repectively. According to the results, it can be concluded that Pb-Protein interaction tends to binding of Pb-Cysteine rather than Pb-Tyrosine

[Interest of toxicological analysis for poisonings].

Science.gov (United States)

Mégarbane, Bruno; Baud, Frédéric J

2008-04-30

The clinical approach of the poisoned patients is mainly based on the analysis of the circumstances of intoxication and the search for toxidromes. Toxicological analysis aims to detect the toxicants or measure their concentrations, in order to confirm the hypothesis of poisoning, to evaluate its severity and to help the follow-up regarding the treatment efficiency. Emergent toxicological analysis appears only useful if the method is specific and the results rapidly obtained. Therefore, systematic screening using immunochesmistry-based tests is not recommended in the situation of emergency. Measurement of blood concentrations of the toxicants is only indicated if it may influence the patient management. However, in the perspective of research, the study of toxicokinetic/toxicodynamic relationships, i.e. the relationships between the toxicant effects and its blood concentrations, may be helpful to understand the inter-individual variability of the response to a toxicant.

Distance learning in toxicology: Resident and remote; Scotland, IPCS, IUPAC, and the world

International Nuclear Information System (INIS)

Duffus, John H.

2005-01-01

Globally, very few college or university chemistry courses incorporate toxicology although public perception of chemicals and the chemical industry as threats to health and the environment has had an adverse effect on chemistry and on the use of its products. The International Union for Pure and Applied Chemistry (IUPAC) through its Commission on Toxicology recognized this and, with the support of the Committee on the Teaching of Chemistry has used the IUPAC web site to promote distance learning in toxicology for chemists. After preparation of a thoroughly refereed consensus Glossary of Terms for Chemists of Terms Used in Toxicology, a textbook Fundamental Toxicology for Chemists and a set of educational modules entitled Essential Toxicology were compiled and put through the normal thorough review procedure of IUPAC before being approved by the organization. There is now an additional Glossary of Terms Used in Toxicokinetics. The modules are freely downloadable in Adobe PDF format and are designed to be used both by educators and by students. Educators are asked to select whatever is appropriate to their students and to use the material as they wish, adding content specifically relevant to their circumstances. For self-study, the web modules have self-assessment questions and model answers. Currently the original Glossary for Chemists of Terms Used in Toxicology is being revised and it is expected that this will lead to further developments. The currently available components of the IUPAC programme may be accessed through the IUPAC website at the Subcommittee on Toxicology and Risk Assessment page: http://www.iupac.org/divisions/VII/VII.C.2/index.html

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....

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)

1990-12-31

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.

Electronic cigarettes in the USA: a summary of available toxicology data and suggestions for the future.

Science.gov (United States)

Orr, Michael S

2014-05-01

To review the available evidence evaluating the toxicological profiles of electronic cigarettes (e-cigarettes) in order to understand the potential impact of e-cigarettes on individual users and the public health. Systematic literature searches were conducted between October 2012 and October 2013 using five electronic databases. Search terms such as 'e-cigarettes' and 'electronic delivery devices' were used to identify the toxicology information for e-cigarettes. As of October 2013, the scientific literature contains very limited information regarding the toxicity of e-cigarettes commercially available in the USA. While some preliminary toxicology data suggests that e-cigarette users are exposed to lower levels of toxicants relative to cigarette smokers, the data available is extremely limited at this time. At present, there is insufficient toxicological data available to perform thorough risk assessment analyses for e-cigarettes; few toxicology studies evaluating e-cigarettes have been conducted to date, and standard toxicological testing paradigms have not been developed for comparing disparate types of tobacco products such as e-cigarettes and traditional cigarettes. Overall, the limited toxicology data on e-cigarettes in the public domain is insufficient to allow a thorough toxicological evaluation of this new type of tobacco product. In the future, the acquisition of scientific datasets that are derived from scientifically robust standard testing paradigms, include comprehensive chemical characterisation of the aerosol, provide information on users' toxicant exposure levels, and from studies replicated by independent researchers will improve the scientific community's ability to perform robust toxicological evaluations of e-cigarettes.

Pharmacological and toxicological evaluation of Urtica dioica.

Science.gov (United States)

Dar, Sabzar Ahmad; Ganai, Farooq Ahmad; Yousuf, Abdul Rehman; Balkhi, Masood-Ul-Hassan; Bhat, Towseef Mohsin; Sharma, Poonam

2013-02-01

Medicinal plants are a largely unexplored source of drug repository. Urtica dioica L. (Urticaceae) is used in traditional medicine to treat diverse conditions. The present study describes the antidiabetic, antiinflammatory, antibacterial activity, and toxicological studies of Urtica dioica. U. dioica leaves were subjected to solvent extraction with hexane, chloroform, ethyl acetate, methanol, and aqueous, respectively, and screened for antidiabetic (300 mg/kg bw by glucose tolerance test; GTT), antiinflammatory (200 mg/kg bw by rat paw edema assay) and antibacterial activities [by disc-diffusion and minimum inhibitory concentration (MIC) assays]. Toxicological studies were carried on Artemia salina and Wistar rats; phytochemical analyses were carried out, using chromatographic and spectroscopic techniques. The aqueous extract of U. dioica (AEUD) significantly (p 1000 μg/mL each on A. salina. Our results showed that the U. dioica leaves are an interesting source of bioactive compounds, justifying their use in folk medicine, to treat various diseases.

Male Reproductive Toxicology: Environmental Exposures vs Reproductive Competence

Science.gov (United States)

Like the lecture this chapter begins with an overview of male reproductive biology and transitions into male reproductive toxicology. It ends with a brief discussion of the strengths and weaknesses in male reproductive toxicology and epidemiology today. This chapter is highly il...

75 FR 74053 - Availability of Final Toxicological Profiles

Science.gov (United States)

2010-11-30

... CONTACT: Ms. Olga Dawkins, Division of Toxicology and Environmental Medicine, Agency for Toxic Substances... Toxicology and Environmental Medicine, Agency for Toxic Substances and Disease Registry, 4700 Buford Highway..., except legal holidays. Availability This notice announces the availability of one new and six updated...

Modern Instrumental Methods in Forensic Toxicology*

Science.gov (United States)

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

2009-01-01

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

LC-MS (/MS) in clinical toxicology screening methods.

Science.gov (United States)

Viette, Véronique; Hochstrasser, Denis; Fathi, Marc

2012-01-01

Toxicological screening is the analysis of biological samples to detect and identify unknown compounds. The high selectivity and sensitivity of liquid chromatography (LC) coupled to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) technology provide an attractive alternative to the current methods (LC-UV, GC/MS, etc.). For these reasons, an increasing number of applications are being published. This paper is a brief overview of LC-MS(/MS) screening methods developed for clinical toxicology in recent years. Various sample treatments, chromatographic separations and detection by mass spectrometry can be combined to obtain screening methods adapted to the constraints and needs of clinical toxicology laboratories. Currently the techniques are in the hands of specialists, mainly in academic institutions. However, the evolution in technology should allow application of these techniques as a tool in toxicology laboratories, thus allowing a more widespread exploitation of their potential.

Computational Toxicology as Implemented by the US EPA ...

Science.gov (United States)

Computational toxicology is the application of mathematical and computer models to help assess chemical hazards and risks to human health and the environment. Supported by advances in informatics, high-throughput screening (HTS) technologies, and systems biology, the U.S. Environmental Protection Agency EPA is developing robust and flexible computational tools that can be applied to the thousands of chemicals in commerce, and contaminant mixtures found in air, water, and hazardous-waste sites. The Office of Research and Development (ORD) Computational Toxicology Research Program (CTRP) is composed of three main elements. The largest component is the National Center for Computational Toxicology (NCCT), which was established in 2005 to coordinate research on chemical screening and prioritization, informatics, and systems modeling. The second element consists of related activities in the National Health and Environmental Effects Research Laboratory (NHEERL) and the National Exposure Research Laboratory (NERL). The third and final component consists of academic centers working on various aspects of computational toxicology and funded by the U.S. EPA Science to Achieve Results (STAR) program. Together these elements form the key components in the implementation of both the initial strategy, A Framework for a Computational Toxicology Research Program (U.S. EPA, 2003), and the newly released The U.S. Environmental Protection Agency's Strategic Plan for Evaluating the T

Toxicology of Marine Mammals: New Developments and Opportunities.

Science.gov (United States)

Weijs, Liesbeth; Zaccaroni, Annalisa

2016-01-01

It is widely recognized that marine mammals are exposed to a wide variety of pollutants, with a weight of evidence indicating impacts on their health. Since hundreds of new chemicals enter the global market every year,the methods, approaches and technologies used to characterize pollution levels or impacts are also in a constant state of flux. However, legal and ethical constraints often limit the type and extent of toxicological research being carried out in marine mammals. Nevertheless, new and emerging in vivo, in vitro as well as in silico research opportunities abound in the field of marine mammal toxicology. In the application of findings to population-, species-, or habitat-related risk assessments, the identification of causal relationships which inform source apportionment is important. This, in turn, is informed by a comprehensive understanding of contaminant classes, profiles and fate overspace and time. Such considerations figure prominently in the design and interpretation of marine mammal (eco)-toxicology research. This mini-review attempts to follow the evolution behind marine mammal toxicology until now,highlight some of the research that has been done and suggest opportunities for future research. This Special Issue will showcase new developments in marine mammal toxicology, approaches for exposure-effect research in risk assessment as well as future opportunities.

Toxicology of Nanomaterials: Permanent interactive learning

Directory of Open Access Journals (Sweden)

Castranova Vince

2009-10-01

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.

Adaptation of the ToxRTool to Assess the Reliability of Toxicology Studies Conducted with Genetically Modified Crops and Implications for Future Safety Testing.

Science.gov (United States)

Koch, Michael S; DeSesso, John M; Williams, Amy Lavin; Michalek, Suzanne; Hammond, Bruce

2016-01-01

To determine the reliability of food safety studies carried out in rodents with genetically modified (GM) crops, a Food Safety Study Reliability Tool (FSSRTool) was adapted from the European Centre for the Validation of Alternative Methods' (ECVAM) ToxRTool. Reliability was defined as the inherent quality of the study with regard to use of standardized testing methodology, full documentation of experimental procedures and results, and the plausibility of the findings. Codex guidelines for GM crop safety evaluations indicate toxicology studies are not needed when comparability of the GM crop to its conventional counterpart has been demonstrated. This guidance notwithstanding, animal feeding studies have routinely been conducted with GM crops, but their conclusions on safety are not always consistent. To accurately evaluate potential risks from GM crops, risk assessors need clearly interpretable results from reliable studies. The development of the FSSRTool, which provides the user with a means of assessing the reliability of a toxicology study to inform risk assessment, is discussed. Its application to the body of literature on GM crop food safety studies demonstrates that reliable studies report no toxicologically relevant differences between rodents fed GM crops or their non-GM comparators.

Toxicological Evaluation of Lactase Derived from Recombinant Pichia pastoris

Science.gov (United States)

Liu, Yifei; Chen, Delong; Luo, Yunbo; Huang, Kunlun; Zhang, Wei; Xu, Wentao

2014-01-01

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. PMID:25184300

Toxicological evaluation of lactase derived from recombinant Pichia pastoris.

Directory of Open Access Journals (Sweden)

Shiying Zou

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

IRIS Toxicological Review of Trichloroethylene (TCE) ...

Science.gov (United States)

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Trichloroethylene (TCE) that when finalized will appear on the Integrated Risk Information System (IRIS) database. The purpose of this Toxicological Review is to provide scientific support and rationale for the hazard and dose-response assessment in IRIS pertaining to chronic exposure to trichloroethylene. It is not intended to be a comprehensive treatise on the chemical or toxicological nature of trichloroethylene.

THE FUTURE OF TOXICOLOGY-PREDICTIVE TOXICOLOGY: AN EXPANDED VIEW OF CHEMICAL TOXICITY

Science.gov (United States)

A chemistry approach to predictive toxicology relies on structure−activity relationship (SAR) modeling to predict biological activity from chemical structure. Such approaches have proven capabilities when applied to well-defined toxicity end points or regions of chemical space. T...

Toxicological Benchmarks for Wildlife

Energy Technology Data Exchange (ETDEWEB)

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

1993-01-01

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

Toxicological Evaluations of Rare Earths and Their Health Impacts to Workers: A Literature Review

Directory of Open Access Journals (Sweden)

Kyung Taek Rim

2013-03-01

Full Text Available In concert with the development of new materials in the last decade, the need for toxicological studies of these materials has been increasing. These new materials include a group of rare earths (RE. The use of RE nanotechnology is being considered in some green applications, to increase their efficiency by using nano-sized RE compounds, and therefore hazard evaluation and risk assessment are highly recommended. This review was conducted through an extensive contemplation of the literatures in toxicology with in vitro and in vivo studies. Major aspects reviewed were the toxicological evaluations of these elements and metallic compounds at the molecular and cellular level, animal and human epidemiological studies and environmental and occupational health impacts on workers. We also discuss the future prospect of industries with appliances using RE together with the significance of preventive efforts for workers’ health. To establish a safe and healthy working environment for RE industries, the use of biomarkers is increasing to provide sustainable measure, due to demand for information about the health risks from unfavorable exposures. Given the recent toxicological results on the exposure of cells, animals and workers to RE compounds, it is important to review the toxicological studies to improve the current understanding of the RE compounds in the field of occupational health. This will help to establish a sustainable, safe and healthy working environment for RE industries.

ICPP radiological and toxicological sabotage analysis

International Nuclear Information System (INIS)

Kubiak, V.R.; Mortensen, F.G.

1995-01-01

In June of 1993, the Department of Energy (DOE) issued Notice 5630.3A, open-quotes Protection of Departmental Facilities Against Radiological and Toxicological Sabotage,close quotes which states that all significant radiological and toxicological hazards at Department facilities must be examined for potential sabotage. This analysis has been completed at the Idaho Chemical Processing Plant (ICPP). The ICPP radiological and toxicological hazards include spent government and commercial fuels, Special Nuclear Materials (SNM), high-level liquid wastes, high-level solid wastes, and process and decontamination chemicals. The analysis effort included identification and assessment of quantities of hazardous materials present at the facility; identification and ranking of hazardous material targets; development of worst case scenarios detailing possible sabotage actions and hazard releases; performance of vulnerability assessments using table top and computer methodologies on credible threat targets; evaluation of potential risks to the public, workers, and the environment; evaluation of sabotage risk reduction options; and selection of cost effective prevention and mitigation options

Distance learning in toxicology: Australia's RMIT program

International Nuclear Information System (INIS)

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

2005-01-01

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; internationalisation of content; interactive participation; and the assessment procedures

Comparative toxicological studies on the effects of internal exposures

International Nuclear Information System (INIS)

Oghiso, Yoichi; Fukuda, Satoshi; Iida, Haruzo; Yamada, Yuji; Kubota, Yoshihisa; Matsuoka, Osamu

1989-01-01

In order to study the toxicological mechanism of transuranic elements, such as plutonium, involved in the induction of pulmonary fibrosis, toxic effects of several inhaled dusts and mineral particles were examined in rats. Pulmonary alveolar macrophage (PAM) was responsible for retention and behavior of inhaled asbestos fibers or silica particles and their transfer to the lymph nodes. PAM exhibited prominent phagocytosis of particles, followed by a significant release of lactic dehydrogenase and beta-glucuronidase. Multinucleated or Ia-positive PAM was frequently observed in rats presenting with pulmonary fibrosis. Pulmonary fibrosis that was induced by inhaled asbestos or silica particles was associated with significant production and release of cytokines. This indicated a close correlation with inflammatory or proliferating responses of fibroblasts and lymphocytes. Such reactions observed in PAM depended on toxicity of particles involved in phagocytosis (i.e., the ability of particles to induce pulmonary fibrosis), suggesting heterogeneity in the population of PAM. (Namekawa, K)

Building bridges between clinical and forensic toxicology laboratories.

Science.gov (United States)

Martin, Bernardino Barcelo; Gomila, Isabel; Noce, Valeria

2018-05-09

Clinical and forensic toxicology can be defined as the two disciplines involved the detection, identification and measurement of xenobiotics in biological and non-biological specimens to help in the diagnosis, treatment, prognosis, prevention of poisonings and to disclose causes and contributory causes of fatal intoxications, respectively. This article explores the close connections between clinical and forensic toxicology in overlapping areas of interest. An update has been carried out of the following seven areas of interest in analytical toxicology: doping control, sudden cardiac death (SCD), brain death, sudden infant death syndrome (SIDS) and Munchausen syndrome by proxy (MSBP), prenatal exposure to drugs and fetal alcohol syndrome (FAS), drug-facilitated crimes (DFC) and intoxications by new psychoactive substances (NPS). While issues such as SCD, SIDS or doping control are investigated mainly in forensic laboratories, other as prenatal exposure to drugs or FAS are mainly treated in clinical laboratories. On the other hand, areas such MSBP, DFC or the intoxications by NPS are of interest in both laboratories. Some of these topics are initially treated in hospital emergency departments, involving clinical laboratories and sometimes lately derived to forensic laboratories. Conversely, cases with initial medical-legal implications and fatalities are directly handled by forensic toxicology, but may trigger further studies in the clinical setting. Many areas of common interest between clinical and forensic laboratories are building bridges between them. The increasing relationships are improving the growth, the reliability and the robustness of both kind of laboratories. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Toxicology research projects directory, 1978. Monthly repts

International Nuclear Information System (INIS)

1978-01-01

The Toxicology Research Projects Directory is a monthly publication of ongoing research projects in toxicology and related fields selected from the files of the Smithsonian Science Information Exchange (SSIE). Each issue lists toxicology-related research projects reported to SSIE during the one-month period preceding that issue. Each of the summaries is categorized by scientific discipline and assigned a unique identification number for cross-referencing from the Directory Indexes--Subject, Investigator, Performing Organization, Supporting Agency, and Master Grant Number. The thirteenth issue consists of Cumulative Indexes for the entire volume with referencing to projects in all of the previous twelve issues. The emphasis of the Directory is on the manifestations of the exposure of man and animals to toxic substances. Projects are classified by toxic agents, research orientation, and areas of environmental concern

Downloadable Computational Toxicology Data

Science.gov (United States)

EPA’s computational toxicology research generates data that investigates the potential harm, or hazard of a chemical, the degree of exposure to chemicals as well as the unique chemical characteristics. This data is publicly available here.

A glance at Spanish embryology and teratology during the XX century through the academic life of Francisco Orts-Llorca (1905-1993).

Science.gov (United States)

Aréchaga, Juan; Jiménez-Collado, Juan; Ruano-Gil, Domingo

2009-01-01

Francisco Ort-Llorca (1905-1993) was one of the most outstanding Spanish embryologists of the XX century. He was disciple of Henri Rouvire in Paris (France), Alfred Fischel in Vienna (Austria), Walther Vogt in Munich (Germany) and Pedro Ara in Madrid (Spain). From 1935, he was professor of Human Anatomy at the Faculty of Medicine of Cadiz, belonged then to the University of Seville (accidentally, in the University of Valencia, during the Spanish Civil War from 1936-1939) and, later on, at the Faculty of Medicine of Madrid (Complutense University) from 1954 to 1975. He was internationally recognized in anatomical sciences and stood out for his contributions to descriptive and experimental Embryology and Teratology, particularly in those aspects connected to the normal and pathological development of the heart and visual organs.

Functional toxicology: tools to advance the future of toxicity testing

Science.gov (United States)

Gaytán, Brandon D.; Vulpe, Chris D.

2014-01-01

The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds—information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes. PMID:24847352

Resolution of aviation forensic toxicology findings with the aid of DNA profiling.

Science.gov (United States)

Chaturvedi, Arvind K; Craft, Kristi J; Kupfer, Doris M; Burian, Dennis; Canfield, Dennis V

2011-03-20

Body components of aviation accident fatalities are often scattered, disintegrated, commingled, contaminated, and/or putrefied at accident scenes. These situations may impose difficulties in victim identification/tissue matching. The prevalence of misidentification in relation to aviation accident forensic toxicology has not been well established. Therefore, the Civil Aerospace Medical Institute (CAMI) toxicology database was searched for the 1998-2008 period for those cases wherein DNA profiling was performed to resolve identity issue of the samples submitted to CAMI for toxicological evaluation. During this period, biological samples from the casualties of a total of 3523 accidents were submitted to CAMI. The submitted samples were primarily from pilots. Out of the 3523 accidents, at least, one fatality had occurred in 3366 (≈ 96%) accidents; thus, these accidents were considered fatal accidents. Accordingly, biological samples from 3319 pilots (3319 of the 3366 accidents) were received at CAMI for toxicological testing. Of these 3319 pilots, 3275 (≈ 99%) were fatally injured. DNA profiling was performed in 15 (≈ 0.5%) of the 3319 accidents. The profiling was conducted upon the requests of families in two accidents, accident investigators in three, and pathologists in four. In six accidents, contradictory toxicological findings led CAMI to initiate DNA profiling. The requests made by families and investigators were primarily triggered by inconsistency between the toxicological results and the history of drug use of the victims, while by pathologists because of commingling of samples. In three (20%) of the 15 accidents, at least one submitted sample was misidentified or mislabeled. The present study demonstrated that the number of aviation accident cases requiring DNA profiling was small and this DNA approach was effectively applied in resolving aviation toxicology findings associated with those accidents. Published by Elsevier Ireland Ltd.

Teratology studies in the rabbit.

Science.gov (United States)

Allais, Linda; Reynaud, Lucie

2013-01-01

The rabbit is generally the non-rodent species or second species after the rat recommended by the regulatory authorities and is part of the package of regulatory reproductive studies for the detection of potential embryotoxic and/or teratogenic effects of pharmaceuticals, chemicals, food additives, and other compounds, including vaccines (see Chapters 1-7).Its availability, practicality in housing and in mating as well as its large size makes the rabbit the preferred choice as a non-rodent species. The study protocols are essentially similar to those established for the rat (Chapter 9), with some particularities. The study designs are well defined in guidelines and are relatively standardized between testing laboratories across the world.As for the rat, large litter sizes and extensive background data in the rabbit are valuable criteria for an optimal assessment of in utero development of the embryo or fetus and for the detection of potential external or internal fetal malformations.

[Continuous challenges in Japanese forensic toxicology practice: strategy to address specific goals].

Science.gov (United States)

Kageura, Mitsuyoshi

2002-09-01

In this paper, the status quo of forensic toxicology in Japan and the West is surveyed and a strategy to address future goals of Japanese forensic toxicology is proposed. Forensic toxicology in the West consists of three main areas--post-mortem forensic toxicology, human-performance forensic toxicology and forensic urine drug testing. In Japan, post-mortem forensic toxicology is practiced in university forensic medicine departments while most of the human-performance forensic toxicology is carried out in police laboratories. However, at least at present, strictly controlled workplace urine drug testing is not being performed, despite the abuse of drugs even by uniformed members of the National Defence Forces and police. For several years, the author has been introducing Western forensic toxicology guidelines and recommendations, translated into Japanese with the help of Western forensic toxicologists, to Japanese forensic toxicologists. Western forensic toxicology practice is at an advanced stage, whereas Japanese practice is in a critical condition and holds many problems awaiting solution, as exemplified by the urine drug testing in police laboratories. There is never any sample left for re-examination by the defence in all cases, though the initial volume of the urine sample available for examination is 30-50 ml. Only one organisation carries out everything from sampling to reporting and, in addition, the parent drug and its metabolites are not quantified. It is clear that the police laboratories do not work within good laboratory practice guidelines, nor do they have quality manuals or standard operating procedures manuals. A basic change in Japanese forensic toxicology practice is now essential. The author strongly recommends that, first of all, Japanese toxicologists should prepare forensic toxicology guidelines based on the Western models. The guidelines would progress the following objectives for forensic toxicology laboratories: 1) to have documented good

Biennal Report 1979/80 of the Institute for Genetics and Toxicology

International Nuclear Information System (INIS)

Hotz, G.

1981-07-01

The research activities of the Genetics and the Toxicology Divisions of the Institute for Genetics and Toxicology of Fissile Materials during the period January 1979 to December 1980 are decribed. In addition to scientific reports on the various research topics the report gives an overview of the external scientific and teaching activities of the staff members during the review period. The main emphasis of the toxicology program has been on studies of the radiotoxicology of the actinides and other heavy metals, especially in relation to chelation therapy and to the development of biochemical and physical methods for investigation of their metabolic behaviour. In the field of radiation genetics most of the interest has been focussed on the mechanisms of gene repair, gene regulation and the molecular biology of tumor viruses. (orig.) [de

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

Science.gov (United States)

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

2016-03-01

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

A comprehensive toxicological evaluation of three adhesives using experimental cigarettes.

Science.gov (United States)

Coggins, Christopher R E; Jerome, Ann M; Lilly, Patrick D; McKinney, Willie J; Oldham, Michael J

2013-01-01

Adhesives are used in several different manufacturing operations in the production of cigarettes. The use of new, "high-speed-manufacture" adhesives (e.g. vinyl acetate based) could affect the smoke chemistry and toxicology of cigarettes, compared with older "low-speed-manufacture" adhesives (e.g. starch based). This study was conducted to determine whether the inclusion of different levels of three adhesives (ethylene vinyl acetate, polyvinyl acetate and starch) in experimental cigarettes results in different smoke chemistry and toxicological responses in in vitro and in vivo assays. A battery of tests (analytical chemistry, in vitro and in vivo assays) was used to compare the chemistry and toxicology of smoke from experimental cigarettes made with different combinations of the three adhesives. Varying levels of the different side-seam adhesives, as well as the transfer of adhesives from packaging materials, were tested. There were differences in some mainstream cigarette smoke constituents as a function of the level of adhesive added to experimental cigarettes and between the tested adhesives. None of these differences translated into statistically significant differences in the in vitro or in vivo assays. The use of newer "high-speed-manufacture" vinyl acetate-based adhesives in cigarettes does not produce toxicological profiles that prevent the adhesives from replacing the older "low-speed-manufacture" adhesives (such as starch).

Computational toxicology: Its essential role in reducing drug attrition.

Science.gov (United States)

Naven, R T; Louise-May, S

2015-12-01

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. © The Author(s) 2015.

The DOE policy for protection against radiological and toxicological sabotage

International Nuclear Information System (INIS)

Hassell, C. Jr.; Callahan, S.; Myers, D.

1995-01-01

In response to a Department of Energy Office of Security Evaluations study on radiological and toxicological sabotage, the Under Secretary of Energy has directed that all departmental elements initiate analyses to determine the extent of radiological and toxicological sabotage threats within the department. To accomplish this, a plan was adopted whereby radioactive and other hazardous materials at DOE sites would be assessed by an interdisciplinary team as to quantities, ranked according to their hazards, subjected to a vulnerability assessment, and appropriate upgrades selected and monitored. This paper is a discussion of those efforts

[Forensic toxicology, a growing scientific discipline].

Science.gov (United States)

Augsburger, Marc; Staub, Christian

2008-07-02

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.

Toxicology study of senna (CAS No. 8013-11-4) in C57BL/6NTAC Mice and toxicology and carcinogenesis study of senna in genetically modified C3B6.129F1/Tac-Trp53tm1Brd haploinsufficient mice (Feed Studies).

Science.gov (United States)

2012-04-01

Senna is used as a stimulant laxative in the management of constipation resulting from opioid use or when treatment with bulking or osmotic agents has failed. Increased use of senna was expected due to the removal of the stimulant laxatives danthron and phenolphthalein from the market. Senna was nominated for study by the Center for Drug Evaluation and Research, United States Food and Drug Administration (FDA) due to the wide use of laxative preparations, positive genotoxicity in vitro for some senna components or metabolites, and unknown carcinogenic potential. Because a 2-year rat study was ongoing by the manufacturer, the FDA requested that the NTP conduct a senna study in the p53(+/-) mouse. In this study, the potential for carcinogenic effects of senna was studied in the C3B6.129F1/Tac-Trp53tm1Brd N12 haploinsufficient (heterozygous F1 p53(+/-)) mouse model as an ongoing goal of the NTP to develop and test model systems for toxicology and carcinogenesis studies, especially those that can provide mechanistic information relative to understanding an agents mode of action. C57BL/6NTac mice were exposed to senna in feed for 5 weeks; heterozygous F1 p53(+/-) mice were exposed to senna in feed for 40 weeks. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes.

Course constructions: A case-base of forensic toxicology.

Science.gov (United States)

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

2017-08-01

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.

Toxicological requirements for risk assessment of shellfish ...

African Journals Online (AJOL)

There is increasing concern by consumers with regard to the health aspects and safety of foodstuffs. Most food additives and contaminants are controlled by regulatory authorities, with Acceptable Daily Intakes (ADIs) having been set on the basis of detailed acute short- and long-term toxicological studies. The situation with ...

A Study of Causes of Readmission Patients Toxicological Ward of the Loghman Hakim Hospital, in Tehran in 2014

Directory of Open Access Journals (Sweden)

R. Ghasempour

2016-02-01

Full Text Available Introduction: Readmission to hospital because of the impact on the cost and quality of hospital care and Impose an additional burden on the healthcare system, Is an important priority for hospital managers. The aim of Study Was causes of readmission patients toxicological ward of the loghman hakim hospital, Research in Tehran. Method: This is an applied cross-sectional retrospective study. Research community included Admissions in 1393 in toxicological ward of the loghman hakim hospital. Research Size based on Morgan is 300 clinical records. Sampling Method was simple randomly. Readmission in the present study in hospitalized form was more than one defined. Demographic data includes (age, gender, marital status, occupation, education and variables related to hospitalization (hospitalization Frequency, length of stay, and poisoning quality, discharge situation, referral and insurance by means of information form was extracted from records. In two level Descriptive statistics (frequency and percentage and inferential statistics (correlation chi-square test, dependent T test and Chi-square test were analyzed using SPSS21 software and hypothesis testing was done. Finding: During the study period300 readmission cases were hospitalized in toxicological ward of the loghman hakim hospital.13/4% patient was readmission. The readmission cause in 41/6% patient was related to family issues. It Can be named respectively emotional, spiritual, and addiction with regard to other topics. The total cost of treating patients was 206521754 Rials. The average cost of stay per patient 10256639 Rials, payment by patient 928136 Rials, and Subsidies health payment by health ministry was 1834370 Rials. Conclusion: The results of this study showed that, several factors may be involved in readmission to hospital patients poisons ,the most important of them can be mentioned in the four ares of family problems, emotional problems, mental problems and addiction.

IRIS Toxicological Review of Trichloroethylene (Interagency Science Consultation Draft)

Science.gov (United States)

On November 3, 2009, the Toxicological Review of Trichloroethylene and the charge to external peer reviewers were released for external peer review and public comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White Hous...

Predictive toxicology in drug safety

National Research Council Canada - National Science Library

Xu, Jinghai J; Urban, Laszlo

2011-01-01

.... 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...

High-resolution mass spectrometry in toxicology: current status and future perspectives.

Science.gov (United States)

Maurer, H H; Meyer, Markus R

2016-09-01

This paper reviews high-resolution mass spectrometry (HRMS) approaches using time-of-flight or Orbitrap techniques for research and application in various toxicology fields, particularly in clinical toxicology and forensic toxicology published since 2013 and referenced in PubMed. In the introduction, an overview on applications of HRMS in various toxicology fields is given with reference to current review articles. Papers concerning HRMS in metabolism, screening, and quantification of pharmaceuticals, drugs of abuse, and toxins in human body samples are critically reviewed. Finally, a discussion on advantages as well as limitations and future perspectives of these methods is included.

[The challenges of the ethics of personalism to clinical toxicology].

Science.gov (United States)

Brusiło, Jerzy

2011-01-01

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?

Does GLP enhance the quality of toxicological evidence for regulatory decisions?

Science.gov (United States)

Borgert, Christopher J.; Becker, Richard A.; Carlton, Betsy D.; Hanson, Mark; Kwiatkowski, Patricia L.; Sue Marty, Mary; McCarty, Lynn S.; Quill, Terry F.; Solomon, Keith; Van Der Kraak, Glen; Witorsch, Raphael J.; Don Yi, Kun

2016-01-01

There is debate over whether the requirements of GLP are appropriate standards for evaluating the quality of toxicological data used to formulate regulations. A group promoting the importance of non-monotonic dose responses for endocrine disruptors contend that scoring systems giving primacy to GLP are biased against non-GLP studies from the literature and are merely record-keeping exercises to prevent fraudulent reporting of data from non-published guideline toxicology studies. They argue that guideline studies often employ insensitive species and outdated methods, and ignore the perspectives of subject-matter experts in endocrine disruption, who should be the sole arbiters of data quality. We believe regulatory agencies should use both non-GLP and GLP studies, that GLP requirements assure fundamental tenets of study integrity not typically addressed by journal peer-review, and that use of standardized test guidelines and GLP promotes consistency, reliability, comparability, and harmonization of various types of studies used by regulatory agencies worldwide. This debate suffers two impediments to progress: a conflation of different phases of study interpretation and levels of data validity, and a misleading characterization of many essential components of GLP and regulatory toxicology. Herein we provide clarifications critical for removing those impediments. PMID:27208076

Renal studies in safety pharmacology and toxicology: A survey conducted in the top 15 pharmaceutical companies.

Science.gov (United States)

Benjamin, Amanda; Gallacher, David J; Greiter-Wilke, Andrea; Guillon, Jean-Michel; Kasai, Cheiko; Ledieu, David; Levesque, Paul; Prelle, Katja; Ratcliffe, Sian; Sannajust, Frederick; Valentin, Jean-Pierre

2015-01-01

With the recent development of more sensitive biomarkers to assess kidney injury preclinically, a survey was designed i) to investigate what strategies are used to investigate renal toxicity in both ICH S7A compliant Safety Pharmacology (SP) studies after a single dose of a compound and within repeat-dose toxicity studies by large pharmaceutical companies today; ii) to understand whether renal SP studies have impact or utility in drug development and/or if it may be more appropriate to assess renal effects after multiple doses of compounds; iii) to ascertain how much mechanistic work is performed by the top 15 largest pharmaceutical companies (as determined by R&D revenue size); iv) to gain an insight into the impact of the validation of DIKI biomarkers and their introduction in the safety evaluation paradigm; and v) to understand the impact of renal/urinary safety study data on progression of projects. Two short anonymous surveys were submitted to SP leaders of the top 15 pharmaceutical companies, as defined by 2012 R&D portfolio size. Fourteen multiple choice questions were designed to explore the strategies used to investigate renal effects in both ICH S7A compliant SP studies and within toxicology studies. A 67% and 60% response rate was obtained in the first and second surveys, respectively. Nine out of ten respondent companies conduct renal excretory measurements (eg. urine analysis) in toxicology studies whereas only five out of ten conduct specific renal SP studies; and all of those 5 also conduct the renal excretory measurements in toxicology studies. These companies measure and/or calculate a variety of parameters as part of these studies, and also on a case by case basis include regulatory qualified and non-qualified DIKI biomarkers. Finally, only one company has used renal/urinary functional data alone to stop a project, whereas the majority of respondents combine renal data with other target organ assessments to form an integrated decision-making set

Aggregated Computational Toxicology Resource (ACTOR)

Data.gov (United States)

U.S. Environmental Protection Agency — The Aggregated Computational Toxicology Resource (ACTOR) is a database on environmental chemicals that is searchable by chemical name and other identifiers, and by...

Counselling pregnant women at the crossroads of Europe and Asia: effect of Teratology Information Service in Turkey.

Science.gov (United States)

Kaplan, Yusuf Cem; Karadaş, Barış; Küçüksolak, Gözde; Ediz, Bartu; Demir, Ömer; Sozmen, Kaan; Nordeng, Hedvig

2017-08-01

Background Previous studies from western countries demonstrated the effectiveness of Teratology Information Service (TIS) counselling in reducing the teratogenic risk perception of pregnant women. Objective To assess whether TIS counselling would be effective in reducing the teratogenic risk perception of the Turkish pregnant women. Setting A TIS (Terafar) operating in a university hospital in Turkey. Methods A cross-sectional survey study. Pregnant women with non-teratogenic medication exposures were asked to assign scores on visual analogue scales (VAS) in response to the questions aiming to measure their teratogenic risk perception. The mean score before and after counselling were compared and the associations with maternal socio-demographic characteristics were analysed using SPSS (Version 20.0). Main outcome measures The differences in the mean scores of the perception regarding the baseline risk of pregnancy, own teratogenic risk and the likelihood of termination of pregnancy before and after counselling and their possible associations with maternal socio-demographic characteristics. Results 102 pregnant women participated in the study. The counselling significantly reduced the mean own teratogenic risk perception score and the mean score for the likelihood of termination of pregnancy whereas the mean baseline risk perception score was not significantly changed. Pregnancy week <8 and the exposed number of active ingredients <3 were significantly associated with the difference in the mean score for the likelihood of termination of pregnancy. Conclusions TIS counselling lowers the teratogenic risk perception of Turkish pregnant women and increases their likelihood to continue the pregnancy as it does in the western countries.

Aggregated Computational Toxicology Online Resource

Data.gov (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...

Good cell culture practices &in vitro toxicology.

Science.gov (United States)

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

2017-12-01

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.

Measuring Impact of EPAs Computational Toxicology Research (BOSC)

Science.gov (United States)

Computational Toxicology (CompTox) research at the EPA was initiated in 2005. Since 2005, CompTox research efforts have made tremendous advances in developing new approaches to evaluate thousands of chemicals for potential health effects. The purpose of this case study is to trac...

Antidiabetic And Toxicological Evaluation Of Aqueous Ethanol Leaf ...

African Journals Online (AJOL)

Secamone afzelii Rhoem is used in ethnomedicine for hepatic diseases, diabetes, venereal diseases, amenorrhoea and toothaches. This present study was aimed at evaluating the antidiabetic activity and to establish the toxicological profile of the plant to confirm its traditional application and justify continuous usage.

The minipig as a platform for new technologies in toxicology

DEFF Research Database (Denmark)

Forster, Roy; Ancian, Philippe; Fredholm, Merete

2010-01-01

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...

Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop.

Science.gov (United States)

Aigner, Achim; Buesen, Roland; Gant, Tim; Gooderham, Nigel; Greim, Helmut; Hackermüller, Jörg; Hubesch, Bruno; Laffont, Madeleine; Marczylo, Emma; Meister, Gunter; Petrick, Jay S; Rasoulpour, Reza J; Sauer, Ursula G; Schmidt, Kerstin; Seitz, Hervé; Slack, Frank; Sukata, Tokuo; van der Vies, Saskia M; Verhaert, Jan; Witwer, Kenneth W; Poole, Alan

2016-12-01

The European Centre for the Ecotoxicology and Toxicology of Chemicals (ECETOC) organised a workshop to discuss the state-of-the-art research on noncoding RNAs (ncRNAs) as biomarkers in regulatory toxicology and as analytical and therapeutic agents. There was agreement that ncRNA expression profiling data requires careful evaluation to determine the utility of specific ncRNAs as biomarkers. To advance the use of ncRNA in regulatory toxicology, the following research priorities were identified: (1) Conduct comprehensive literature reviews to identify possibly suitable ncRNAs and areas of toxicology where ncRNA expression profiling could address prevailing scientific deficiencies. (2) Develop consensus on how to conduct ncRNA expression profiling in a toxicological context. (3) Conduct experimental projects, including, e.g., rat (90-day) oral toxicity studies, to evaluate the toxicological relevance of the expression profiles of selected ncRNAs. Thereby, physiological ncRNA expression profiles should be established, including the biological variability of healthy individuals. To substantiate the relevance of key ncRNAs for cell homeostasis or pathogenesis, molecular events should be dose-dependently linked with substance-induced apical effects. Applying a holistic approach, knowledge on ncRNAs, 'omics and epigenetics technologies should be integrated into adverse outcome pathways to improve the understanding of the functional roles of ncRNAs within a regulatory context. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Frequency of forensic toxicological analysis in external cause deaths among nursing home residents: an analysis of trends.

Science.gov (United States)

Aitken, Georgia; Murphy, Briony; Pilgrim, Jennifer; Bugeja, Lyndal; Ranson, David; Ibrahim, Joseph Elias

2017-03-01

There is a paucity of research examining the utility of forensic toxicology in the investigation of premature external cause deaths of residents in nursing homes. The aim of this study is to describe the frequency and characteristics of toxicological analysis conducted in external cause (injury-related) deaths amongst nursing home residents in Victoria, Australia. This study was a retrospective cohort study examining external cause deaths among nursing home residents during the period July 1, 2000 to December 31, 2012 in Victoria, Australia, using the National Coronial Information System (NCIS). The variables examined comprised: sex, age group, year-of-death, cause and manner of death. One-third of deaths among nursing home residents in Victoria resulted from external causes (n = 1296, 33.3%) of which just over one-quarter (361, 27.9%) underwent toxicological analysis as part of the medical death investigation. The use of toxicological analysis varied by cause of death with a relatively low proportion conducted in deaths from unintentional falls (n = 286, 24.9%) and choking (n = 36, 40.4%). The use of toxicological analysis decreased as the decedents age increased. Forensic toxicology has the potential to contribute to improving our understanding of premature deaths in nursing home residents however it remains under used and is possibly undervalued.

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)

2004-09-15

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.

IRIS Toxicological Review of Trichloroacetic Acid (Tca) (Final ...

Science.gov (United States)

EPA has finalized the Toxicological Review of Trichloroacetic Acid: 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. The draft Toxicological Review of Trichloroacetic Acid provides scientific support and rationale for the hazard identification and dose-response assessment pertaining to chronic exposure to trichloroacetic acid.

Comparison of toxicological and radiological aspects of K basins sludge

International Nuclear Information System (INIS)

RITTMANN, P.D.

1999-01-01

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

Toxicological aspects of fuel and exhaust gas

International Nuclear Information System (INIS)

Avella, F.

1993-01-01

Some aspects concerning fuels (gasoline) and gas exhaust vehicle emissions toxicology are briefly examined in light of the results reported in recent literature on this argument. Many experimental studies carried out on animals and men turn out incomplete and do not allow thorough evaluations, for every aspect, of the risk to which men and the environment are subjected

IRIS Toxicological Review of Benzo[a]pyrene (Interagency ...

Science.gov (United States)

In January 2017, EPA finalized the IRIS assessment of Benzo[a]pyrene. The Toxicological Review was reviewed internally by EPA and by other federal agencies and White House Offices before public release. Consistent with the May 2009 IRIS assessment development process, all written comments on IRIS assessments submitted by other federal agencies and White House Offices are made publicly available. Accordingly, interagency comments and the interagency science discussion materials provided to other agencies, including interagency review drafts of the IRIS Toxicological Review of Benzo[a]pyrene are posted on this site. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for benzo[a]pyrene (BaP). The outcome of this project is an updated Toxicological Review and IRIS Summary for BaP that will be entered into the IRIS database.

Opportunity for Collaboration Between Radiation Injury Treatment Network Centers and Medical Toxicology Specialists.

Science.gov (United States)

Davlantes, Elizabeth; Shartar, Samuel; Venero, Jennifer; Steck, Alaina; Langston, Amelia; Kazzi, Ziad N

2017-08-01

The Radiation Injury Treatment Network (RITN) comprises >50 centers across the United States that are poised to care for victims of a radiation emergency. The network is organized around bone marrow transplant centers because these facilities excel in both radiation medicine and the care of patients with severe bone marrow depression. A radiation emergency may cause not only irradiation from an external source but also internal contamination with radioactive material. Because medical toxicologists are trained in radiation injury management and have expertise in the management of internal contamination, RITN centers may benefit from partnerships with medical toxicology resources, which may be located at academic medical centers, hospital inpatient clinical services, outpatient clinics, or poison control centers. We determined the locations of existing RITN centers and assessed their proximity to various medical toxicology resources, including medical toxicology fellowship programs, inpatient toxicology services, outpatient toxicology clinics, and poison control centers. Data were derived from publicly available Internet sources in March 2015. The majority of RITN centers do not have a medical toxicology fellowship, an inpatient toxicology service, or an outpatient toxicology clinic within the same institution. Fifty-seven percent of RITN centers have at least one of these resources located in the same city, however, and 73% of centers have at least one of these resources or a poison control center within the same city. Ninety-five percent of RITN centers have at least one medical toxicology resource within the state. Most RITN centers are located in the same city as at least one medical toxicology resource. Establishing relationships between RITN centers and medical toxicologists needs to be explored further.

Green Toxicology: a strategy for sustainable chemical and material development.

Science.gov (United States)

Crawford, Sarah E; Hartung, Thomas; Hollert, Henner; Mathes, Björn; van Ravenzwaay, Bennard; Steger-Hartmann, Thomas; Studer, Christoph; Krug, Harald F

2017-01-01

Green Toxicology refers to the application of predictive toxicology in the sustainable development and production of new less harmful materials and chemicals, subsequently reducing waste and exposure. Built upon the foundation of "Green Chemistry" and "Green Engineering", "Green Toxicology" aims to shape future manufacturing processes and safe synthesis of chemicals in terms of environmental and human health impacts. Being an integral part of Green Chemistry, the principles of Green Toxicology amplify the role of health-related aspects for the benefit of consumers and the environment, in addition to being economical for manufacturing companies. Due to the costly development and preparation of new materials and chemicals for market entry, it is no longer practical to ignore the safety and environmental status of new products during product development stages. However, this is only possible if toxicologists and chemists work together early on in the development of materials and chemicals to utilize safe design strategies and innovative in vitro and in silico tools. This paper discusses some of the most relevant aspects, advances and limitations of the emergence of Green Toxicology from the perspective of different industry and research groups. The integration of new testing methods and strategies in product development, testing and regulation stages are presented with examples of the application of in silico, omics and in vitro methods. Other tools for Green Toxicology, including the reduction of animal testing, alternative test methods, and read-across approaches are also discussed.

Operational Toxicology Research

Science.gov (United States)

2006-08-01

techniques for perchlorate in water, groundwater, soil and biological matrices such as blood, urine, milk . thyroid and other tissues required for...toxicity when they are inhaled or ingested and they are irritating to the skin and mucus membranes (Committee on Toxicology, 1996). When compared to...the data collected. Develop analytical techniques for perchlorate in water, groundwater, soil, and biological matrices such as blood, urine, milk

Toxicological benchmarks for wildlife: 1996 Revision

International Nuclear Information System (INIS)

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

1996-06-01

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

Toxicological benchmarks for wildlife: 1996 Revision

Energy Technology Data Exchange (ETDEWEB)

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

1996-06-01

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.

Aspects of matrix effects in applications of liquid chromatography-mass spectrometry to forensic and clinical toxicology--a review.

Science.gov (United States)

Peters, Frank T; Remane, Daniela

2012-06-01

In the last decade, liquid chromatography coupled to (tandem) mass spectrometry (LC-MS(-MS)) has become a versatile technique with many routine applications in clinical and forensic toxicology. However, it is well-known that ionization in LC-MS(-MS) is prone to so-called matrix effects, i.e., alteration in response due to the presence of co-eluting compounds that may increase (ion enhancement) or reduce (ion suppression) ionization of the analyte. Since the first reports on such matrix effects, numerous papers have been published on this matter and the subject has been reviewed several times. However, none of the existing reviews has specifically addressed aspects of matrix effects of particular interest and relevance to clinical and forensic toxicology, for example matrix effects in methods for multi-analyte or systematic toxicological analysis or matrix effects in (alternative) matrices almost exclusively analyzed in clinical and forensic toxicology, for example meconium, hair, oral fluid, or decomposed samples in postmortem toxicology. This review article will therefore focus on these issues, critically discussing experiments and results of matrix effects in LC-MS(-MS) applications in clinical and forensic toxicology. Moreover, it provides guidance on performance of studies on matrix effects in LC-MS(-MS) procedures in systematic toxicological analysis and postmortem toxicology.

Interpretation of postmortem forensic toxicology results for injury prevention research.

Science.gov (United States)

Drummer, Olaf H; Kennedy, Briohny; Bugeja, Lyndal; Ibrahim, Joseph Elias; Ozanne-Smith, Joan

2013-08-01

Forensic toxicological data provides valuable insight into the potential contribution of alcohol and drugs to external-cause deaths. There is a paucity of material that guides injury researchers on the principles that need to be considered when examining the presence and contribution of alcohol and drugs to these deaths. This paper aims to describe and discuss strengths and limitations of postmortem forensic toxicology sample selection, variations in analytical capabilities and data interpretation for injury prevention research. Issues to be considered by injury researchers include: the circumstances surrounding death (including the medical and drug use history of the deceased person); time and relevant historical factors; postmortem changes (including redistribution and instability); laboratory practices; specimens used; drug concentration; and attribution of contribution to death. This paper describes the range of considerations for testing and interpreting postmortem forensic toxicology, particularly when determining impairment or toxicity as possible causal factors in injury deaths. By describing these considerations, this paper has application to decisions about study design and case inclusion in injury prevention research, and to the interpretation of research findings.

Docking-based classification models for exploratory toxicology studies on high-quality estrogenic experimental data

Science.gov (United States)

Background: Exploratory toxicology is a new emerging research area whose ultimate mission is that of protecting human health and environment from risks posed by chemicals. In this regard, the ethical and practical limitation of animal testing has encouraged the promotion of compu...

IRIS Toxicological Review of Methanol (Noncancer) (Interagency Science Discussion Draft)

Science.gov (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...

Toward the Rational Use of Exposure Information in Mixtures Toxicology

Science.gov (United States)

Of all the disciplines of toxicology, perhaps none is as dependent on exposure information as Mixtures Toxicology. Identifying real world mixtures and replicating them in the laboratory (or in silico) is critical to understanding their risks. Complex mixtures such as cigarett...

Toxicological Effects of Cigarette Smoke on Some Biochemical ...

African Journals Online (AJOL)

It is believed that while normal people may suffer complications of active and passive cigarette smoking, diabetes patients may suffer more. This study therefore aimed at investigating the toxicological effects of cigarette smoke on some biochemical parameters of alloxan-induced diabetic rats. Adult male Wistar rats (n ...

Liquid chromatography-mass spectrometry in occupational toxicology: a novel approach to the study of biotransformation of industrial chemicals.

Science.gov (United States)

Manini, Paola; Andreoli, Roberta; Niessen, Wilfried

2004-11-26

Biological monitoring and biomarkers are used in occupational toxicology for a more accurate risk assessment of occupationally exposed people. Appropriate and validated biomarkers of internal dose, like urinary metabolites, besides to be positively correlated with external exposure, have a predictive value to the risk of adverse effects. The application of liquid chromatography-mass spectrometry (LC-MS) in occupational and environmental toxicology, although relatively recent, has been demonstrated valid in the determination of traditional biomarkers of exposure, as well as in metabolism studies aimed at investigating minor metabolic routes and new more specific biomarkers. This review presents selected applications of LC-MS to the study of the metabolism of industrial chemicals, like n-hexane, benzene and other aromatic hydrocarbons, styrene and other monomers employed in plastic industry, as well as to other chemicals used in working environments, like pesticides used by farmers, and antineoplastic agents prepared by hospital personnel. Analytical and pre-analytical factors, which affect quantitative determination of urinary metabolites, i.e. sample preparation, matrix effect, ion suppression, use of internal standards, and calibration, are emphasized.

Chick embryo chorioallantoic membrane (CAM): an alternative predictive model in acute toxicological studies for anti-cancer drugs.

Science.gov (United States)

Kue, Chin Siang; Tan, Kae Yi; Lam, May Lynn; Lee, Hong Boon

2015-01-01

The chick embryo chorioallantoic membrane (CAM) is a preclinical model widely used for vascular and anti-vascular effects of therapeutic agents in vivo. In this study, we examine the suitability of CAM as a predictive model for acute toxicology studies of drugs by comparing it to conventional mouse and rat models for 10 FDA-approved anticancer drugs (paclitaxel, carmustine, camptothecin, cyclophosphamide, vincristine, cisplatin, aloin, mitomycin C, actinomycin-D, melphalan). Suitable formulations for intravenous administration were determined before the average of median lethal dose (LD50) and median survival dose (SD(50)) in the CAM were measured and calculated for these drugs. The resultant ideal LD(50) values were correlated to those reported in the literature using Pearson's correlation test for both intravenous and intraperitoneal routes of injection in rodents. Our results showed moderate correlations (r(2)=0.42 - 0.68, PLD(50) values obtained using the CAM model with LD(50) values from mice and rats models for both intravenous and intraperitoneal administrations, suggesting that the chick embryo may be a suitable alternative model for acute drug toxicity screening before embarking on full toxicological investigations in rodents in development of anticancer drugs.

Radiological/toxicological sabotage assessments at the Savannah River Site

International Nuclear Information System (INIS)

Johnson, H.D.; Pascal, M.D.; Richardson, D.L.

1995-01-01

This paper describes the methods being employed by Westinghouse Savannah River Company (WSRC) to perform graded assessments of radiological and toxicological sabotage vulnerability at Savannah River Site (SRS) facilities. These assessments are conducted to ensure that effective measures are in place to prevent, mitigate, and respond to a potential sabotage event which may cause an airborne release of radiological/toxicological material, causing an adverse effect on the health and safety of employees, the public, and the environment. Department of Energy (DOE) Notice 5630.3A, open-quotes Protection of Departmental Facilities Against Radiological and Toxicological Sabotage,close quotes and the associated April 1993 DOE-Headquarters guidance provide the requirements and outline an eight-step process for hazardous material evaluation. The process requires the integration of information from a variety of disciplines, including safety, safeguards and security, and emergency preparedness. This paper summarizes WSRC's approach towards implementation of the DOE requirements, and explains the inter-relationships between the Radiological and Toxicological Assessments developed using this process, and facility Hazard Assessment Reports (HAs), Safety Analysis Reports (SARs), and Facility Vulnerability Assessments (VAs)

American College of Medical Toxicology

Science.gov (United States)

... Publications Journal of Medical Toxicology About ACMT About Us History of ACMT ACMT Fact Sheet Strategic Plan ACMT ... Policies IJMT JMT Editorial Board About ACMT About Us History of ACMT ACMT Fact Sheet Strategic Plan ACMT ...

La toxicología en la atención primaria de salud

Directory of Open Access Journals (Sweden)

Jesús Martínez Cabrera

1995-06-01

Full Text Available Se expone la función que debe desempeñar la toxicología en Cuba para contribuir al logro de la meta de Salud para todos en el año 2000, así como los factores que condicionan el surgimiento de la toxicología preventiva. Se expresan los principales elementos que debe conocer el médico de la familia sobre toxicología y la necesidad de ampliar la interacción en el terreno docente, asistencial e investigativo entre la toxicología y el nivel de atención primaria de salud.

Historical perspectives on cadmium toxicology

International Nuclear Information System (INIS)

Nordberg, Gunnar F.

2009-01-01

The first health effects of cadmium (Cd) were reported already in 1858. Respiratory and gastrointestinal symptoms occurred among persons using Cd-containing polishing agent. The first experimental toxicological studies are from 1919. Bone effects and proteinuria in humans were reported in the 1940's. After World War II, a bone disease with fractures and severe pain, the itai-itai disease, a form of Cd-induced renal osteomalacia, was identified in Japan. Subsequently, the toxicokinetics and toxicodynamics of Cd were described including its binding to the protein metallothionein. International warnings of health risks from Cd-pollution were issued in the 1970's. Reproductive and carcinogenic effects were studied at an early stage, but a quantitative assessment of these effects in humans is still subject to considerable uncertainty. The World Health Organization in its International Program on Chemical Safety, WHO/IPCS (1992) (Cadmium. Environmental Health Criteria Document 134, IPCS. WHO, Geneva, 1-280.) identified renal dysfunction as the critical effect and a crude quantitative evaluation was presented. In the 1990's and 2000 several epidemiological studies have reported adverse health effects, sometimes at low environmental exposures to Cd, in population groups in Japan, China, Europe and USA (reviewed in other contributions to the present volume). The early identification of an important role of metallothionein in cadmium toxicology formed the basis for recent studies using biomarkers of susceptibility to development of Cd-related renal dysfunction such as gene expression of metallothionein in peripheral lymphocytes and autoantibodies against metallothionein in blood plasma. Findings in these studies indicate that very low exposure levels to cadmium may give rise to renal dysfunction among sensitive subgroups of human populations such as persons with diabetes.

Triennial report 1981-83 of the Institute for Genetics and for Toxicology

International Nuclear Information System (INIS)

Hotz, G.

1984-07-01

The scientific activity of the Divisions of Genetics and of Toxicology of the Institute for Genetics and for Toxicology during the period January 1981 to December 1983 is described. In addition to reports on the various research topics this second 'Report' also gives an overview of the external scientific and teaching activities of the staff members during the period. In the field of radiation genetics most of the interest has been focussed on the mechanisms of gene repair, gene regulation and the molecular biology of tumor viruses in human and other mammalian cells. The main emphasis of the long term toxicology program has been on studies of radiotoxicology of the actinides and other heavy metals, especially in relation to chelation therapy and to the development of biochemical and physical methods for investigation of their metabolic behaviour. (orig.) [de

Recent developments in analytical toxicology : for better or for worse

NARCIS (Netherlands)

de Zeeuw, RA

1998-01-01

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,

In silico toxicology for the pharmaceutical sciences

International Nuclear Information System (INIS)

Valerio, Luis G.

2009-01-01

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

Diagnostic yield of hair and urine toxicology testing in potential child abuse cases.

Science.gov (United States)

Stauffer, Stephanie L; Wood, Stephanie M; Krasowski, Matthew D

2015-07-01

Detection of drugs in a child may be the first objective finding that can be reported in cases of suspected child abuse. Hair and urine toxicology testing, when performed as part of the initial clinical evaluation for suspected child abuse or maltreatment, may serve to facilitate the identification of at-risk children. Furthermore, significant environmental exposure to a drug (considered by law to constitute child abuse in some states) may be identified by toxicology testing of unwashed hair specimens. In order to determine the clinical utility of hair and urine toxicology testing in this population we performed a retrospective chart review on all children for whom hair toxicology testing was ordered at our academic medical center between January 2004 and April 2014. The medical records of 616 children aged 0-17.5 years were reviewed for injury history, previous medication and illicit drug use by caregiver(s), urine drug screen result (if performed), hair toxicology result, medication list, and outcome of any child abuse evaluation. Hair toxicology testing was positive for at least one compound in 106 cases (17.2%), with unexplained drugs in 82 cases (13.3%). Of these, there were 48 cases in which multiple compounds (including combination of parent drugs and/or metabolites within the same drug class) were identified in the sample of one patient. The compounds most frequently identified in the hair of our study population included cocaine, benzoylecgonine, native (unmetabolized) tetrahydrocannabinol, and methamphetamine. There were 68 instances in which a parent drug was identified in the hair without any of its potential metabolites, suggesting environmental exposure. Among the 82 cases in which hair toxicology testing was positive for unexplained drugs, a change in clinical outcome was noted in 71 cases (86.5%). Urine drug screens (UDS) were performed in 457 of the 616 reviewed cases. Of these, over 95% of positive UDS results could be explained by iatrogenic drug

Drug shortages: Implications for medical toxicology.

Science.gov (United States)

Mazer-Amirshahi, Maryann; Hawley, Kristy L; Zocchi, Mark; Fox, Erin; Pines, Jesse M; Nelson, Lewis S

2015-07-01

Drug shortages have significantly increased over the past decade. There are limited data describing how shortages impact medical toxicology of drugs. To characterize drug shortages affecting the management of poisoned patients. Drug shortage data from January 2001 to December 2013 were obtained from the University of Utah Drug Information Service. Shortage data for agents used to treat poisonings were analyzed. Information on drug type, formulation, reason for shortage, shortage duration, marketing, and whether the drug was available from a single source was collected. The availability of a substitute therapy and whether substitutes were in shortage during the study period were also investigated. Of 1,751 shortages, 141 (8.1%) impacted drugs used to treat poisoned patients, and as of December 2013, 21 (14.9%) remained unresolved. New toxicology shortages increased steadily from the mid-2000s, reaching a high of 26 in 2011. Median shortage duration was 164 days (interquartile range: 76-434). Generic drugs were involved in 85.1% of shortages and 41.1% were single-source products. Parenteral formulations were often involved in shortages (89.4%). The most common medications in shortage were sedative/hypnotics (15.6%). An alternative agent was available for 121 (85.8%) drugs; however, 88 (72.7%) alternatives were also affected by shortages at some point during the study period. When present, the most common reasons reported were manufacturing delays (22.0%) and supply/demand issues (17.0%). Shortage reason was not reported for 48.2% of drugs. Toxicology drug shortages are becoming increasingly prevalent, which can result in both suboptimal treatment and medication errors from using less familiar alternatives. Drug shortages affected a substantial number of critical agents used in the management of poisoned patients. Shortages were often of long duration and for drugs without alternatives. Providers caring for poisoned patients should be aware of current shortages and

Nano-technology and nano-toxicology.

Science.gov (United States)

Maynard, Robert L

2012-01-01

Rapid developments in nano-technology are likely to confer significant benefits on mankind. But, as with perhaps all new technologies, these benefits are likely to be accompanied by risks, perhaps by new risks. Nano-toxicology is developing in parallel with nano-technology and seeks to define the hazards and risks associated with nano-materials: only when risks have been identified they can be controlled. This article discusses the reasons for concern about the potential effects on health of exposure to nano-materials and relates these to the evidence of the effects on health of the ambient aerosol. A number of hypotheses are proposed and the dangers of adopting unsubstantiated hypotheses are stressed. Nano-toxicology presents many challenges and will need substantial financial support if it is to develop at a rate sufficient to cope with developments in nano-technology.

Nuclear toxicology at CEA

International Nuclear Information System (INIS)

Giustranti, C.

2001-01-01

CEA (French commission of atomic energy) has launched a new program dedicated to the study of the transfer of heavy metals and some radionuclides from environment to living beings. The substances that will be studied, are those that are involved in research, medical activities, and in nuclear industry. It means iodine, technetium, trans-uranides (uranium and plutonium), fission products (iodine, cesium), carbon, cobalt, boron and beryllium. This program is composed of 2 axis: the first one concerns the bio-geo-chemical cycles that are involved in transfer and the second axis deals with the detoxication processes that appear in animal and man cells. This program will rely on the strong competencies of CEA in chemistry, radiochemistry, biology, physiology and toxicology. (A.C.)

An audit of the toxicology findings in 555 medico-legal autopsies finds manner of death changed in 5 cases.

Science.gov (United States)

Langlois, Neil E I; Gilbert, John D; Heath, Karen J; Winskog, Calle; Kostakis, Chris

2013-03-01

An audit of toxicological analysis in Coronial autopsies performed at Forensic Science South Australia was conducted on the cases of three pathologists. Toxicological analysis had been performed in 555 (68 %) from a total of 815 autopsies. It was found that the proffered manner of death was changed from the provisional report (provided immediately after the post-mortem examination) in five cases (just under 1 %) as a consequence of the toxicological findings. This is a limited study as it is retrospective, not all cases had toxicological analysis and the findings are constrained by the range of the substances that could be detected. Nonetheless, the audit supports the application of toxicological analysis in medico-legal death investigation and suggests that an inclusive policy should be adopted.

Toxicological benchmarks for wildlife: 1994 Revision

International Nuclear Information System (INIS)

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

1994-09-01

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

Toxicological benchmarks for wildlife: 1994 Revision

Energy Technology Data Exchange (ETDEWEB)

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

1994-09-01

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.

Postmortem Biochemistry and Toxicology

Directory of Open Access Journals (Sweden)

Robert Flanagan

2017-04-01

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.

Pulmonary toxicology of respirable particles

International Nuclear Information System (INIS)

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

1980-09-01

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

Surprises and omissions in toxicology

Czech Academy of Sciences Publication Activity Database

Rašková, H.; Zídek, Zdeněk

2004-01-01

Roč. 12, - (2004), S94-S96 ISSN 1210-7778. [Inderdisciplinary Czech-Slovak Toxicological Conference /8./. Praha, 03.09.2004-05.09.2004] Institutional research plan: CEZ:AV0Z5008914 Keywords : bacterial toxins Subject RIV: FR - Pharmacology ; Medidal Chemistry

Distance learning and toxicology: New horizons for Paracelsus

International Nuclear Information System (INIS)

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

2005-01-01

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

76 FR 23323 - Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM)

Science.gov (United States)

2011-04-26

... the scientific validation and regulatory acceptance of toxicological and safety testing methods that... DEPARTMENT OF HEALTH AND HUMAN SERVICES Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) AGENCY: National Toxicology Program (NTP), National Institute of...

Aerospace toxicology overview: aerial application and cabin air quality.

Science.gov (United States)

Chaturvedi, Arvind K

2011-01-01

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

Recent trends in analytical procedures in forensic toxicology.

Science.gov (United States)

Van Bocxlaer, Jan F

2005-12-01

Forensic toxicology is a very demanding discipline,heavily dependent on good analytical techniques. That is why new trends appear continuously. In the past years. LC-MS has revolutionized target compound analysis and has become the trend, also in toxicology. In LC-MS screening analysis, things are less straightforward and several approaches exist. One promising approach based on accurate LC-MSTOF mass measurements and elemental formula based library searches is discussed. This way of screening has already proven its applicability but at the same time it became obvious that a single accurate mass measurement lacks some specificity when using large compound libraries. CE too is a reemerging approach. The increasingly polar and ionic molecules encountered make it a worthwhile addition to e.g. LC, as illustrated for the analysis of GHB. A third recent trend is the use of MALDI mass spectrometry for small molecules. It is promising for its ease-of-use and high throughput. Unfortunately, re-ports of disappointment but also accomplishment, e.g. the quantitative analysis of LSD as discussed here, alternate, and it remains to be seen whether MALDI really will establish itself. Indeed, not all new trends will prove themselves but the mere fact that many appear in the world of analytical toxicology nowadays is, in itself, encouraging for the future of (forensic) toxicology.

Acute Toxicological Effects of Crude Oil On Haematological And ...

African Journals Online (AJOL)

The acute toxicological effects of Brass blend of crude oil on the haemoglobin concentration, and Liver functions in the Guinea pig were studied. 25 Guinea pigs divided into five animals per group were used for the study. They were divided into 5 groups. One group served as a control group, while the others received ...

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

Directory of Open Access Journals (Sweden)

Alexios eKoutsoukas

2016-03-01

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

75 FR 25867 - National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative...

Science.gov (United States)

2010-05-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM.... Bucher, Associate Director, National Toxicology Program. [FR Doc. 2010-10958 Filed 5-7-10; 8:45 am...

Risk, Uncertainty and Precaution in Science: The Threshold of the Toxicological Concern Approach in Food Toxicology.

Science.gov (United States)

Bschir, Karim

2017-04-01

Environmental risk assessment is often affected by severe uncertainty. The frequently invoked precautionary principle helps to guide risk assessment and decision-making in the face of scientific uncertainty. In many contexts, however, uncertainties play a role not only in the application of scientific models but also in their development. Building on recent literature in the philosophy of science, this paper argues that precaution should be exercised at the stage when tools for risk assessment are developed as well as when they are used to inform decision-making. The relevance and consequences of this claim are discussed in the context of the threshold of the toxicological concern approach in food toxicology. I conclude that the approach does not meet the standards of an epistemic version of the precautionary principle.

Regulatory aspects of teratology: role of the Food and Drug Administration

International Nuclear Information System (INIS)

Kelsey, F.O.

1982-01-01

The Food and Drug Administration is a scientific regulatory agency whose consumer protection activities cover a wide range of products including foods and additives, and pesticide residues on foods; drugs; cosmetics; medical devices; and radiation-emitting electronic products. Amongst its concerns is the possible teratogen effects of regulated products to which the pregnant woman is exposed. The policies and programs of the agency directed toward reducing such risks to the unborn are reviewed. These measures include guidelines for animal reproduction studies and for clinical trials involving women to childbearing potential; labeling of products to disclose known or possible harm to the fetus or embryo; surveillance procedures designed to detect previously unsuspected adverse effects of marketed products; research activities designed to develop better understanding of developmental toxicology and improved techniques for detecting embryocidal and embryotoxic effects; and educational efforts directed both to professionals and the public regarding hazards to the unborn of agency-regulated products

Toxicological evaluation of clay minerals and derived nanocomposites: a review.

Science.gov (United States)

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

2015-04-01

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

Indoor and outdoor airborne particles : an in vitro study on mutagenic potential and toxicological implications

NARCIS (Netherlands)

Houdt, van J.J.

1988-01-01

Introduction

Air pollution components are present as gases and as particulate matter. As particle deposition takes place in various parts of the respiratory system particulate matter may have other toxicological implications than gaseous pollutants, which all may

Immunological and toxicological risk assessment of e-cigarettes.

Science.gov (United States)

Kaur, Gagandeep; Pinkston, Rakeysha; Mclemore, Benathel; Dorsey, Waneene C; Batra, Sanjay

2018-03-31

Knowledge of the long-term toxicological and immunological effects of e-cigarette (e-cig) aerosols remains elusive due to the relatively short existence of vaping. Therefore, we performed a systematic search of articles published in public databases and analysed the research evidence in order to provide critical information regarding e-cig safety. Electronic nicotine delivery systems (or e-cigs) are an alternative to traditional cigarettes for the delivery of nicotine and are typically filled with glycerol or propylene glycol-based solutions known as e-liquids. Though present in lower quantities, e-cig aerosols are known to contain many of the harmful chemicals found in tobacco smoke. However, due to the paucity of experimental data and contradictory evidence, it is difficult to draw conclusive outcomes regarding toxicological, immunological and clinical impacts of e-cig aerosols. Excessive vaping has been reported to induce inflammatory responses including mitogen-activated protein kinase, Janus tyrosine kinase/signal transducer and activator of transcription and nuclear factor-κB signalling, similar to that induced by tobacco smoke. Based on recent evidence, prolonged exposure to some constituents of e-cig aerosols might result in respiratory complications such as asthma, chronic obstructive pulmonary disease and inflammation. Future studies are warranted that focus on establishing correlations between e-cig types, generations and e-liquid flavours and immunological and toxicological profiles to broaden our understanding about the effects of vaping. Copyright ©ERS 2018.

Immunological and toxicological risk assessment of e-cigarettes

Directory of Open Access Journals (Sweden)

Gagandeep Kaur

2018-02-01

Full Text Available Knowledge of the long-term toxicological and immunological effects of e-cigarette (e-cig aerosols remains elusive due to the relatively short existence of vaping. Therefore, we performed a systematic search of articles published in public databases and analysed the research evidence in order to provide critical information regarding e-cig safety. Electronic nicotine delivery systems (or e-cigs are an alternative to traditional cigarettes for the delivery of nicotine and are typically filled with glycerol or propylene glycol-based solutions known as e-liquids. Though present in lower quantities, e-cig aerosols are known to contain many of the harmful chemicals found in tobacco smoke. However, due to the paucity of experimental data and contradictory evidence, it is difficult to draw conclusive outcomes regarding toxicological, immunological and clinical impacts of e-cig aerosols. Excessive vaping has been reported to induce inflammatory responses including mitogen-activated protein kinase, Janus tyrosine kinase/signal transducer and activator of transcription and nuclear factor-κB signalling, similar to that induced by tobacco smoke. Based on recent evidence, prolonged exposure to some constituents of e-cig aerosols might result in respiratory complications such as asthma, chronic obstructive pulmonary disease and inflammation. Future studies are warranted that focus on establishing correlations between e-cig types, generations and e-liquid flavours and immunological and toxicological profiles to broaden our understanding about the effects of vaping.

Eco-toxicological studies of diesel and biodiesel fuels in aerated soil

International Nuclear Information System (INIS)

Lapinskiene, Asta; Martinkus, Povilas; Rebzdaite, Vilija

2006-01-01

The goal of this study was to compare diesel fuel to biodiesel fuel by determining the toxicity of analyzed materials and by quantitatively evaluating the microbial transformation of these materials in non-adapted aerated soil. The toxicity levels were determined by measuring the respiration of soil microorganisms as well as the activity of soil dehydrogenases. The quantitative evaluation of biotransformation of analyzed materials was based on the principle of balancing carbon in the following final products: (a) carbon dioxide; (b) humus compounds; (c) the remainder of non-biodegraded analyzed material; and (d) intermediate biodegradation products and the biomass of microorganisms. The results of these studies indicate that diesel fuel has toxic properties at concentrations above 3% (w/w), while biodiesel fuel has none up to a concentration of 12% (w/w). The diesel fuel is more resistant to biodegradation and produces more humus products. The biodiesel is easily biotransformed. - The comparison of diesel and biodiesel fuels' eco-toxicological parameters in non-adapted aerated soil is relevant when considering the effects of these substances on the environment in cases of accidental spills

77 FR 22321 - National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative...

Science.gov (United States)

2012-04-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP) Interagency Center for... (HTS) Assays for the Tox21 Initiative AGENCY: Division of the National Toxicology Program (DNTP...: April 5, 2012. John R. Bucher, Associate Director, National Toxicology Program. [FR Doc. 2012-8942 Filed...

Blood transcriptomics: applications in toxicology

Science.gov (United States)

Joseph, Pius; Umbright, Christina; Sellamuthu, Rajendran

2015-01-01

The number of new chemicals that are being synthesized each year has been steadily increasing. While chemicals are of immense benefit to mankind, many of them have a significant negative impact, primarily owing to their inherent chemistry and toxicity, on the environment as well as human health. In addition to chemical exposures, human exposures to numerous non-chemical toxic agents take place in the environment and workplace. Given that human exposure to toxic agents is often unavoidable and many of these agents are found to have detrimental human health effects, it is important to develop strategies to prevent the adverse health effects associated with toxic exposures. Early detection of adverse health effects as well as a clear understanding of the mechanisms, especially at the molecular level, underlying these effects are key elements in preventing the adverse health effects associated with human exposure to toxic agents. Recent developments in genomics, especially transcriptomics, have prompted investigations into this important area of toxicology. Previous studies conducted in our laboratory and elsewhere have demonstrated the potential application of blood gene expression profiling as a sensitive, mechanistically relevant and practical surrogate approach for the early detection of adverse health effects associated with exposure to toxic agents. The advantages of blood gene expression profiling as a surrogate approach to detect early target organ toxicity and the molecular mechanisms underlying the toxicity are illustrated and discussed using recent studies on hepatotoxicity and pulmonary toxicity. Furthermore, the important challenges this emerging field in toxicology faces are presented in this review article. PMID:23456664

Evaluation of miR-122 as a Serum Biomarker for Hepatotoxicity in Investigative Rat Toxicology Studies.

Science.gov (United States)

Sharapova, T; Devanarayan, V; LeRoy, B; Liguori, M J; Blomme, E; Buck, W; Maher, J

2016-01-01

MicroRNAs are short noncoding RNAs involved in regulation of gene expression. Certain microRNAs, including miR-122, seem to have ideal properties as biomarkers due to good stability, high tissue specificity, and ease of detection across multiple species. Recent reports have indicated that miR-122 is a highly liver-specific marker detectable in serum after liver injury. The purpose of the current study was to assess the performance of miR-122 as a serum biomarker for hepatotoxicity in short-term (5-28 days) repeat-dose rat toxicology studies when benchmarked against routine clinical chemistry and histopathology. A total of 23 studies with multiple dose levels of experimental compounds were examined, and they included animals with or without liver injury and with various hepatic histopathologic changes. Serum miR-122 levels were quantified by reverse transcription quantitative polymerase chain reaction. Increases in circulating miR-122 levels highly correlated with serum elevations of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH). Statistical analysis showed that miR-122 outperformed ALT as a biomarker for histopathologically confirmed liver toxicity and was equivalent in performance to AST and GLDH. Additionally, an increase of 4% in predictive accuracy was obtained using a multiparameter approach incorporating miR-122 with ALT, AST, and GLDH. In conclusion, serum miR-122 levels can be utilized as a biomarker of hepatotoxicity in acute and subacute rat toxicology studies, and its performance can rival or exceed those of standard enzyme biomarkers such as the liver transaminases. © The Author(s) 2015.

In Silico Toxicology – Non-Testing Methods

Science.gov (United States)

Raunio, Hannu

2011-01-01

In silico toxicology in its broadest sense means “anything that we can do with a computer in toxicology.” Many different types of in silico methods have been developed to characterize and predict toxic outcomes in humans and environment. The term non-testing methods denote grouping approaches, structure–activity relationship, and expert systems. These methods are already used for regulatory purposes and it is anticipated that their role will be much more prominent in the near future. This Perspective will delineate the basic principles of non-testing methods and evaluate their role in current and future risk assessment of chemical compounds. PMID:21772821

Mind the Gap! A Journey towards Computational Toxicology.

Science.gov (United States)

Mangiatordi, Giuseppe Felice; Alberga, Domenico; Altomare, Cosimo Damiano; Carotti, Angelo; Catto, Marco; Cellamare, Saverio; Gadaleta, Domenico; Lattanzi, Gianluca; Leonetti, Francesco; Pisani, Leonardo; Stefanachi, Angela; Trisciuzzi, Daniela; Nicolotti, Orazio

2016-09-01

Computational methods have advanced toxicology towards the development of target-specific models based on a clear cause-effect rationale. However, the predictive potential of these models presents strengths and weaknesses. On the good side, in silico models are valuable cheap alternatives to in vitro and in vivo experiments. On the other, the unconscious use of in silico methods can mislead end-users with elusive results. The focus of this review is on the basic scientific and regulatory recommendations in the derivation and application of computational models. Attention is paid to examine the interplay between computational toxicology and drug discovery and development. Avoiding the easy temptation of an overoptimistic future, we report our view on what can, or cannot, realistically be done. Indeed, studies of safety/toxicity represent a key element of chemical prioritization programs carried out by chemical industries, and primarily by pharmaceutical companies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Application of the threshold of toxicological concern (TTC) concept to the safety assessment of chemically complex food matrices

NARCIS (Netherlands)

Rennen, M.A.J.; Koster, S.; Krul, C.A.M.; Houben, G.F.

2011-01-01

The toxicological assessment of chemically complex food matrices (CCFM) usually is very time consuming, expensive and uses many animal studies. Improvements to obtain a more efficient assessment process remain limited as long as we retain traditional approaches to toxicological risk assessment. New

Collaborative development of predictive toxicology applications.

Science.gov (United States)

Hardy, Barry; Douglas, Nicki; Helma, Christoph; Rautenberg, Micha; Jeliazkova, Nina; Jeliazkov, Vedrin; Nikolova, Ivelina; Benigni, Romualdo; Tcheremenskaia, Olga; Kramer, Stefan; Girschick, Tobias; Buchwald, Fabian; Wicker, Joerg; Karwath, Andreas; Gütlein, Martin; Maunz, Andreas; Sarimveis, Haralambos; Melagraki, Georgia; Afantitis, Antreas; Sopasakis, Pantelis; Gallagher, David; Poroikov, Vladimir; Filimonov, Dmitry; Zakharov, Alexey; Lagunin, Alexey; Gloriozova, Tatyana; Novikov, Sergey; Skvortsova, Natalia; Druzhilovsky, Dmitry; Chawla, Sunil; Ghosh, Indira; Ray, Surajit; Patel, Hitesh; Escher, Sylvia

2010-08-31

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-activity relationship modelling of REACH

FORUM - FutureTox II: In vitro Data and In Silico Models for Predictive Toxicology

Science.gov (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...

A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity

Directory of Open Access Journals (Sweden)

Josinete B. Vieira

2014-07-01

Full Text Available The Density Functional Theory (DFT method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with different degrees of cytotoxicity against the human hepatocellular carcinoma HepG2 line. Principal component analysis (PCA and hierarchical cluster analysis (HCA were employed to select the most important descriptors related to anticancer activity. The significant molecular descriptors related to the compounds with anticancer activity were the ALOGPS_log, Mor29m, IC5 and GAP energy. The Pearson correlation between activity and most important descriptors were used for the regression partial least squares (PLS and principal component regression (PCR models built. The regression PLS and PCR were very close, with variation between PLS and PCR of R2 = ±0.0106, R2ajust = ±0.0125, s = ±0.0234, F(4,11 = ±12.7802, Q2 = ±0.0088, SEV = ±0.0132, PRESS = ±0.4808 and SPRESS = ±0.0057. These models were used to predict the anticancer activity of eight new artemisinin compounds (test set with unknown activity, and for these new compounds were predicted pharmacokinetic properties: human intestinal absorption (HIA, cellular permeability (PCaCO2, cell permeability Maden Darby Canine Kidney (PMDCK, skin permeability (PSkin, plasma protein binding (PPB and penetration of the blood-brain barrier (CBrain/Blood, and toxicological: mutagenicity and carcinogenicity. The test set showed for two new artemisinin compounds satisfactory results for anticancer activity and pharmacokinetic and toxicological properties. Consequently, further studies need be done to evaluate the different proposals as well as their actions, toxicity, and potential use for treatment of cancers.

77 FR 60707 - National Toxicology Program Board of Scientific Counselors; Announcement of Meeting; Request for...

Science.gov (United States)

2012-10-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Toxicology Program... announces the next meeting of the National Toxicology Program (NTP) Board of Scientific Counselors (BSC... such as toxicology, pharmacology, pathology, biochemistry, epidemiology, risk assessment...

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

Science.gov (United States)

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

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

78 FR 24762 - National Toxicology Program Board of Scientific Counselors; Announcement of Meeting; Request for...

Science.gov (United States)

2013-04-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Toxicology Program... announces the next meeting of the National Toxicology Program (NTP) Board of Scientific Counselors (BSC... authorities knowledgeable in fields such as toxicology, pharmacology, pathology, biochemistry, epidemiology...

Toxicological applications of neutron-activation analysis

International Nuclear Information System (INIS)

Cross, J.D.; Dale, I.M.; Smith, H.

1975-01-01

Thermal neutron-activation analysis is recognised as a useful tool for trace element studies in toxicology. This paper describes some recent applications of the technique to three elements when ingested by people in excess of normal intake Two of the elements (copper and chromium) are essential to life and one (bromine) is as yet unclassified. Three deaths were investiagted and trace element levels compared with normal levels from healthy subjects in the same geographical area who had died as a result of violence. (author)

Network chemistry, network toxicology, network informatics, and network behavioristics: A scientific outline

OpenAIRE

WenJun Zhang

2016-01-01

In present study, I proposed some new sciences: network chemistry, network toxicology, network informatics, and network behavioristics. The aims, scope and scientific foundation of these sciences are outlined.

Pilot-Reported Beta-Blockers Identified by Forensic Toxicology Analysis of Postmortem Specimens

Science.gov (United States)

2017-01-01

This study compared beta-blockers reported by pilots with the medications found by postmortem toxicology analysis of specimens received from fatal aviation accidents between 1999 and 2015. Several studies have compared drugs using the standard approa...

Retrospective Mining of Toxicology Data to Discover Multispecies Effects: Anemia as a Case Study (SOT)

Science.gov (United States)

In vivo toxicology data is subject to multiple sources of uncertainty: observer severity bias (a pathologist may record only more severe effects and ignore less severe ones); dose spacing issues (this can lead to missing data, e.g. if a severe effect has a less severe precursor, ...

75 FR 57027 - National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative...

Science.gov (United States)

2010-09-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM); Availability of Interagency..., Associate Director, National Toxicology Program. [FR Doc. 2010-23262 Filed 9-16-10; 8:45 am] BILLING CODE...

75 FR 32942 - National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative...

Science.gov (United States)

2010-06-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM): Availability of the Biennial... Toxicology Program. [FR Doc. 2010-13952 Filed 6-9-10; 8:45 am] BILLING CODE 4140-01-P ...

Results of a Wildlife Toxicology Workshop held by the Smithsonian Institution ? Identification and prioritization of problem statements

Science.gov (United States)

Grim, K.C.; Fairbrother, A.; Monfort, S.; Tan, S.; Rattner, B.A.; Gerould, S.; Beasley, V.; Aguirre, A.; Rowles, T.

2007-01-01

On March 13-15, 2007 nearly 50 scientists and administrators from the US and Canada participated in a Smithsonian-sponsored Wildlife Toxicology Workshop. Invitees were from academic, government, conservation and the private organizations and were selected to represent the diverse disciplines that encompass wildlife toxicology. The workshop addressed scientific and policy issues, strengths and weaknesses of current research strategies, interdisciplinary and science-based approaches in the study of complex contaminant issues, mechanisms for disseminating data to policy-makers, and the development of a partner network to meet the challenges facing wildlife toxicology over the next decade. Prior to the meeting, participants were asked to submit issues they deemed to be of highest concern which shaped four thematic groups for discussion: Wildlife Toxicology in Education, Risk Assessment, Multiple Stressors/Complex Mixtures, and Sub-Lethal to Population-Level Effects. From these discussion groups, 18 problem statements were developed and prioritized outlining what were deemed the most important issues to address now and into the future. Along with each problem statement participants developed potential solutions and action steps geared to move each issue forward. The workshop served as a stepping stone for action in the field of wildlife toxicology. These problem statements and the resulting action items are presented to the inter-disciplinary wildlife toxicology community for adoption, and future work and action items in these areas are encouraged. The workshop outcome looks to generate conversation and collaboration that will lead to the development of innovative research, future mechanisms for funding, workshops, working groups, and listserves within the wildlife toxicology community.

A Graduate Program in Toxicology: Administrative and Educational Benefits of Interdepartmental Management.

Science.gov (United States)

Masten, Lawrence W.

1979-01-01

The University of Mississippi School of Pharmacy's Department of Pharmacology offers masters and doctoral programs in toxicology. Its programs and toxicology courses are described, and the administration of these interdisciplinary programs within one department is discussed. (JMD)

Finding toxicological information: An approach for occupational health professionals

Directory of Open Access Journals (Sweden)

Franco Giuliano

2008-08-01

Full Text Available Abstract Background It can be difficult for occupational health professionals to assess which toxicological databases available on the Internet are the most useful for answering their questions. Therefore we evaluated toxicological databases for their ability to answer practical questions about exposure and prevention. We also propose recommended practices for searching for toxicological properties of chemicals. Methods We used a systematic search to find databases available on the Internet. Our criteria for the databases were the following: has a search engine, includes factual information on toxic and hazardous chemicals harmful for human health, and is free of charge. We developed both a qualitative and a quantitative rating method, which was used by four independent assessors to determine appropriateness, the quality of content, and ease of use of the database. Final ratings were based on a consensus of at least two evaluators. Results Out of 822 results we found 21 databases that met our inclusion criteria. Out of these 21 databases 14 are administered in the US, five in Europe, one in Australia, and one in Canada. Nine are administered by a governmental organization. No database achieved the maximum score of 27. The databases GESTIS, ESIS, Hazardous Substances Data Bank, TOXNET and NIOSH Pocket Guide to Chemical Hazards all scored more than 20 points. The following approach was developed for occupational health professionals searching for the toxicological properties of chemicals: start with the identity of the chemical; then search for health hazards, exposure route and measurement; next the limit values; and finally look for the preventive measures. Conclusion A rating system of toxicological databases to assess their value for occupational health professionals discriminated well between databases in terms of their appropriateness, quality of information, and ease of use. Several American and European databases yielded high scores and

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

2013-07-01

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)

PIXE applications to the toxicological field

International Nuclear Information System (INIS)

Santos, C.E.I. dos; Dias, J.F.; Jobim, P.F.C.; Yoneama, M.L.; Andrade, V.M.; Amaral, L.; Silva, J. da

2013-01-01

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)

Developmental toxicology of radon exposures

International Nuclear Information System (INIS)

Sikov, M.R.; Cross, F.T.; Mast, T.J.; Palmer, H.E.; James, A.C.; Thrall, K.D.

1992-01-01

Concerns about hazards associated with radon exposure in dwellings may be especially relevant to pregnant women, many of whom spend substantial amounts of time in their homes. There are few data concerning the placental transfer and fetoplacental distribution of inhaled radon and decay products or their effects on the conceptus. We performed a study in rats to determine if prenatal effects could be produced by prolonged inhalation exposures to high concentrations of radon throughout gestation. A group of 43 pregnant rats was exposed 18 h d -1 , at a rate of 124 working level months (WLM) per day, from 6 to 19 days of gestation (dg), of radon and daughters adsorbed onto ore dust. A group of 26 pregnant rats from the same shipment was exposed to a filtered-air atmosphere as controls. At 20 dg, the rats were removed from the chambers, killed, and necropsied. The fetuses were evaluated for the presence of toxic effects, which included detailed teratology protocols. These exposures did not produce detectable reproductive toxicity nor teratogenic change. Two other rats were removed from the radon chambers during the last day of exposure, and their tissues were analyzed to determine the distribution of radioactivity and for dosimetry. Samples from these rats suggested that the dose rates to the placenta were roughly threefold those to the fetus but were similar to those to the liver and femur of the pregnant rats. These data indicate that the dose to the conceptus from the decay of placentally transferred radon and its progeny is more important than the contribution of translocated decay products. Translocated radon decay products are an important source of radiation doses to placental structures, however, and may have most of the radioactivity content at birth

EU Framework 6 Project: Predictive Toxicology (PredTox)-overview and outcome

International Nuclear Information System (INIS)

Suter, Laura; Schroeder, Susanne; Meyer, Kirstin; Gautier, Jean-Charles; Amberg, Alexander; Wendt, Maria; Gmuender, Hans; Mally, Angela; Boitier, Eric; Ellinger-Ziegelbauer, Heidrun; Matheis, Katja; Pfannkuch, Friedlieb

2011-01-01

In this publication, we report the outcome of the integrated EU Framework 6 Project: Predictive Toxicology (PredTox), including methodological aspects and overall conclusions. Specific details including data analysis and interpretation are reported in separate articles in this issue. The project, partly funded by the EU, was carried out by a consortium of 15 pharmaceutical companies, 2 SMEs, and 3 universities. The effects of 16 test compounds were characterized using conventional toxicological parameters and 'omics' technologies. The three major observed toxicities, liver hypertrophy, bile duct necrosis and/or cholestasis, and kidney proximal tubular damage were analyzed in detail. The combined approach of 'omics' and conventional toxicology proved a useful tool for mechanistic investigations and the identification of putative biomarkers. In our hands and in combination with histopathological assessment, target organ transcriptomics was the most prolific approach for the generation of mechanistic hypotheses. Proteomics approaches were relatively time-consuming and required careful standardization. NMR-based metabolomics detected metabolite changes accompanying histopathological findings, providing limited additional mechanistic information. Conversely, targeted metabolite profiling with LC/GC-MS was very useful for the investigation of bile duct necrosis/cholestasis. In general, both proteomics and metabolomics were supportive of other findings. Thus, the outcome of this program indicates that 'omics' technologies can help toxicologists to make better informed decisions during exploratory toxicological studies. The data support that hypothesis on mode of action and discovery of putative biomarkers are tangible outcomes of integrated 'omics' analysis. Qualification of biomarkers remains challenging, in particular in terms of identification, mechanistic anchoring, appropriate specificity, and sensitivity.

Comparative BioInformatics and Computational Toxicology

Science.gov (United States)

Reflecting the numerous changes in the field since the publication of the previous edition, this third edition of Developmental Toxicology focuses on the mechanisms of developmental toxicity and incorporates current technologies for testing in the risk assessment process.

[Application of liquid chromatography-high resolution mass spectrometry in toxicological screening].

Science.gov (United States)

Li, Xiao-Wen; Shen, Bao-Hua; Zhuo, Xian-Yi

2011-10-01

Due to the diversity of toxicologically relevant substances, the uncertainty of target compounds and the specificity of samples, toxicological screening techniques have always been valued by the forensic toxicologists. Depending on its powerful separation ability, superhigh resolution and accurate mass measurement, combined with the two levels spectrum database matching and abundance ratio of isotope ion, the liquid chromatography-high resolution mass spectrometry (LC-HRMS) analyzers have increasingly advantage in screening and identification of chemical compound. This review focuses on the applications of LC-HRMS in screening and identification of drug-of-abuse, prescription drugs, pesticide and stimulant. The prospect of LC-HRMS in forensic toxicology analysis is also included.

IRIS Toxicological Review of Thallium and Compounds ...

Science.gov (United States)

Thallium compounds are used in the semiconductor industry, the manufacture of optic lenses and low-melting glass, low-temperature thermometers, alloys, electronic devices, mercury lamps, fireworks, and imitation germs, and clinically as an imaging agent in the diagnosis of certain tumors. EPA's assessment of noncancer health effects and carcinogenic potential of thallium compounds was last prepared and added to the IRIS database between 1988 and 1990. The IRIS program is preparing an assessment that will incorporate current health effects information available for thallium and compounds, and current risk assessment methods. The IRIS assessment for thallium compounds 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 in humans and experimental systems. The assessment will present reference values for the noncancer effects of thallium compounds (RfD and Rfc), and a cancer assessment. The Toxicological Review and IRIS Summary have been subject to Agency review, Interagency review, and external scientific peer review. The final product will reflect the Agency opinion on the overall toxicity of thallium and compounds. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for thallium and compounds. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effec

NMR-based metabolomic studies on the toxicological effects of cadmium and copper on green mussels Perna viridis

International Nuclear Information System (INIS)

Wu Huifeng; Wang Wenxiong

2010-01-01

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.

Evaluating the Impact of the U.S. National Toxicology Program: A Case Study on Hexavalent Chromium.

Science.gov (United States)

Xie, Yun; Holmgren, Stephanie; Andrews, Danica M K; Wolfe, Mary S

2017-02-01

Evaluating the impact of federally funded research with a broad, methodical, and objective approach is important to ensure that public funds advance the mission of federal agencies. We aimed to develop a methodical approach that would yield a broad assessment of National Toxicology Program's (NTP's) effectiveness across multiple sectors and demonstrate the utility of the approach through a case study. A conceptual model was developed with defined activities, outputs (products), and outcomes (proximal, intermediate, distal) and applied retrospectively to NTP's research on hexavalent chromium (CrVI). Proximal outcomes were measured by counting views of and requests for NTP's products by external stakeholders. Intermediate outcomes were measured by bibliometric analysis. Distal outcomes were assessed through Web and LexisNexis searches for documents related to legislation or regulation changes. The approach identified awareness of NTP's work on CrVI by external stakeholders (proximal outcome) and citations of NTP's research in scientific publications, reports, congressional testimonies, and legal and policy documents (intermediate outcome). NTP's research was key to the nation's first-ever drinking water standard for CrVI adopted by California in 2014 (distal outcome). By applying this approach to a case study, the utility and limitations of the approach were identified, including challenges to evaluating the outcomes of a research program. This study identified a broad and objective approach for assessing NTP's effectiveness, including methodological needs for more thorough and efficient impact assessments in the future. Citation: Xie Y, Holmgren S, Andrews DMK, Wolfe MS. 2017. Evaluating the impact of the U.S. National Toxicology Program: a case study on hexavalent chromium. Environ Health Perspect 125:181-188; http://dx.doi.org/10.1289/EHP21.

Accelerating the Development of 21st-Century Toxicology: Outcome of a Human Toxicology Project Consortium Workshop

Science.gov (United States)

Stephens, Martin L.; Barrow, Craig; Andersen, Melvin E.; Boekelheide, Kim; Carmichael, Paul L.; Holsapple, Michael P.; Lafranconi, Mark

2012-01-01

The U.S. National Research Council (NRC) report on “Toxicity Testing in the 21st century” calls for a fundamental shift in the way that chemicals are tested for human health effects and evaluated in risk assessments. The new approach would move toward in vitro methods, typically using human cells in a high-throughput context. The in vitro methods would be designed to detect significant perturbations to “toxicity pathways,” i.e., key biological pathways that, when sufficiently perturbed, lead to adverse health outcomes. To explore progress on the report’s implementation, the Human Toxicology Project Consortium hosted a workshop on 9–10 November 2010 in Washington, DC. The Consortium is a coalition of several corporations, a research institute, and a non-governmental organization dedicated to accelerating the implementation of 21st-century Toxicology as aligned with the NRC vision. The goal of the workshop was to identify practical and scientific ways to accelerate implementation of the NRC vision. The workshop format consisted of plenary presentations, breakout group discussions, and concluding commentaries. The program faculty was drawn from industry, academia, government, and public interest organizations. Most presentations summarized ongoing efforts to modernize toxicology testing and approaches, each with some overlap with the NRC vision. In light of these efforts, the workshop identified recommendations for accelerating implementation of the NRC vision, including greater strategic coordination and planning across projects (facilitated by a steering group), the development of projects that test the proof of concept for implementation of the NRC vision, and greater outreach and communication across stakeholder communities. PMID:21948868

CEBS: a comprehensive annotated database of toxicological data

Science.gov (United States)

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

2017-01-01

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

FISH PHYSIOLOGY, TOXICOLOGY, AND WATER QUALITY:

Science.gov (United States)

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...

Evolution of Computational Toxicology-from Primitive ...

Science.gov (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

The rat incisor in toxicologic pathology

NARCIS (Netherlands)

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

1996-01-01

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

Evolution of toxicology information systems

Energy Technology Data Exchange (ETDEWEB)

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

1990-12-31

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.

Collaborative development of predictive toxicology applications

Directory of Open Access Journals (Sweden)

Hardy Barry

2010-08-01

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

"Seeing is believing": perspectives of applying imaging technology in discovery toxicology.

Science.gov (United States)

Xu, Jinghai James; Dunn, Margaret Condon; Smith, Arthur Russell

2009-11-01

Efficiency and accuracy in addressing drug safety issues proactively are critical in minimizing late-stage drug attritions. Discovery toxicology has become a specialty subdivision of toxicology seeking to effectively provide early predictions and safety assessment in the drug discovery process. Among the many technologies utilized to select safer compounds for further development, in vitro imaging technology is one of the best characterized and validated to provide translatable biomarkers towards clinically-relevant outcomes of drug safety. By carefully applying imaging technologies in genetic, hepatic, and cardiac toxicology, and integrating them with the rest of the drug discovery processes, it was possible to demonstrate significant impact of imaging technology on drug research and development and substantial returns on investment.

Reflections on the Origins and Evolution of Genetic Toxicology and the Environmental Mutagen Society

Energy Technology Data Exchange (ETDEWEB)

Wassom, John S. [Oak Ridge National Laboratory (Retired); Malling, Heinrich V. [National Institute of Environmental Health Sciences (NIEHS); Sankaranarayanan, K. [Leiden University; Lu, Po-Yung [ORNL

2010-01-01

This article traces the development of the field of mutagenesis and its metamorphosis into the research area we now call genetic toxicology. In 1969 this transitional event led to the founding of the Environmental Mutagen Society (EMS). The charter of this new Society was to encourage interest in and study of mutagens in the human environment, particularly as these may be of concern to public health. As the mutagenesis field unfolded and expanded, the lexicon changed and new wording appeared to better describe this evolving area of research. The term genetic toxicology was coined and became an important subspecialty of the broad area of toxicology. Genetic toxicology is now set for a thorough reappraisal of its methods, goals, and priorities to meet the challenges of the 21st Century. To better understand these challenges, we have revisited the primary goal that the EMS founders had in mind for the Society s main mission and objective, namely, the quantitative assessment of genetic (hereditary) risks to human populations exposed to environmental agents. We also have reflected upon some of the seminal events over the last 40 years that have influenced the advancement of the genetic toxicology discipline and the extent to which the Society s major goal and allied objectives have been achieved. Additionally, we have provided suggestions on how EMS can further advance the science of genetic toxicology in the postgenome era. Chronicling all events and publications that influenced the development of the mutagenesis and genetic toxicology research area for this article was not possible, but some key happenings that contributed to the field s development have been reviewed. Events that led to the origin of EMS are also presented in celebration of the Society s 40th anniversary. Any historical accounting will have perceived deficiencies. Key people, publications, or events that some readers may feel have had significant impact on development of the subject under review may

The U.S. National Library of Medicine's Toxicology and Environmental Health Information Program

International Nuclear Information System (INIS)

Wexler, Philip

2004-01-01

For nearly 40 years, the National Library of Medicine's (NLM) Toxicology and Environmental Health Information Program (TEHIP) has been a significant leader in organizing and providing public access to an extensive storehouse of toxicological information through its online databases. With the advent of the Internet, TEHIP has expanded its role to also serve as a pre-eminent portal to toxicological information worldwide. Its primary databases reside within the web-based TOXNET system, and include the scientifically peer-reviewed Hazardous Substances Data Bank (HSDB), the U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) and Toxics Release Inventory, the National Cancer Institute's Chemical Carcinogenesis Research Information System (CCRIS) and the TOXLINE file of over 3 million bibliographic references. TEHIP's ChemIDplus is an extensive chemical dictionary that extends beyond simple nomenclature to offer displays of molecular structures and links from particular chemicals to other databases containing more information. Specialty files in occupational safety and health, and household products have recently been added to TEHIP's suite of resources. Additional databases in risk assessment, drugs, toxicology education, and global resources, are under development. ''Special Topics'' pages lead users to structured summaries and links in areas such as arsenic, chemical warfare agents, biological warfare, and West Nile Virus. A database on alternatives to the use of live animals, a three-module toxicology tutor, and a glossary of terms in toxicology are among TEHIP's other information aids, as well an increasing commitment to serving consumers, as witnessed by the animated ToxTown program. Outside the sphere of TEHIP, NLM offers additional databases, such as PubMed, of significant value to toxicology researchers

Safety and toxicology assessment of chicken breast for high-dose irradiation

International Nuclear Information System (INIS)

Zhu Jiating; Feng Min; Yan Jianmin; Yang Ping; Wang Dening; Gao Meixu; Ha Yiming; Liu Chunquan

2011-01-01

Feeding wholesomeness tests of irradiated chicken breast were studied by using acute oral toxicology, Ames, micronucleus of born marrow cell, sperm shape abnormality in mice and 30 d feeding test. The LD 50 of all the rats and mice were more than 10 g/kg · BW, which means that the pet foods belonged to actually non-toxic grade; ames test, and the tests of micronucleus of born marrow cell, sampan shape abnormality in mice were all negative results; 30 d feeding test in rats demonstrated that it had no distinctive effects on routine blood, body weight and biochemical index. It is concluded that pet foods irradiated up to 25 kGy high dose were no safety and toxicology problems. (authors)

Toxicological and radiological safety of chicken meat irradiated with 7.5 MeV X-rays

Science.gov (United States)

Song, Beom-Seok; Lee, Yunjong; Park, Jong-Heum; Kim, Jae-Kyung; Park, Ha-Young; Kim, Dong-Ho; Kim, Chang-Jong; Kang, Il-Jun

2018-03-01

This study was conducted to evaluate the toxicological and radiological safety of chicken meat that had been irradiated at 30 kGy with 7.5 MeV X-rays. In a sub-chronic toxicity study, ICR mice were fed X-ray-irradiated chicken meat at 2500 mg/kg body weight daily for 90 days, and no mortality or abnormal clinical signs were observed throughout the study period. However, several hematological and serum biochemical parameters of the ICR mice differed significantly from those in the control group; nevertheless, the observed values were all within the normal range for the respective parameters. In addition, no toxicological effects were determined in male or female mice. Furthermore, no differences in gamma-ray spectrometric patterns were detected between the non-irradiated and irradiated samples, indicating that the radioactivity induced by 7.5 MeV X-ray irradiation was below the detection limit. These results tentatively suggest that chicken meat irradiated with 7.5 MeV X-rays would be safe for human consumption in terms of toxicology and radiology.

Toxicological risk assessment and prioritization of drinking water relevant contaminants of emerging concern.

Science.gov (United States)

Baken, Kirsten A; Sjerps, Rosa M A; Schriks, Merijn; van Wezel, Annemarie P

2018-06-13

Toxicological risk assessment of contaminants of emerging concern (CEC) in (sources of) drinking water is required to identify potential health risks and prioritize chemicals for abatement or monitoring. In such assessments, concentrations of chemicals in drinking water or sources are compared to either (i) health-based (statutory) drinking water guideline values, (ii) provisional guideline values based on recent toxicity data in absence of drinking water guidelines, or (iii) generic drinking water target values in absence of toxicity data. Here, we performed a toxicological risk assessment for 163 CEC that were selected as relevant for drinking water. This relevance was based on their presence in drinking water and/or groundwater and surface water sources in downstream parts of the Rhine and Meuse, in combination with concentration levels and physicochemical properties. Statutory and provisional drinking water guideline values could be derived from publically available toxicological information for 142 of the CEC. Based on measured concentrations it was concluded that the majority of substances do not occur in concentrations which individually pose an appreciable human health risk. A health concern could however not be excluded for vinylchloride, trichloroethene, bromodichloromethane, aniline, phenol, 2-chlorobenzenamine, mevinphos, 1,4-dioxane, and nitrolotriacetic acid. For part of the selected substances, toxicological risk assessment for drinking water could not be performed since either toxicity data (hazard) or drinking water concentrations (exposure) were lacking. In absence of toxicity data, the Threshold of Toxicological Concern (TTC) approach can be applied for screening level risk assessment. The toxicological information on the selected substances was used to evaluate whether drinking water target values based on existing TTC levels are sufficiently protective for drinking water relevant CEC. Generic drinking water target levels of 37 μg/L for

IRIS Toxicological Review of n-Butanol (Interagency Science ...

Science.gov (United States)

On September 8, 2011, the Toxicological Review of n-Butanol (External Review Draft) was released for external peer review and public comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offices before public release. In the new IRIS process, introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments with EPA's response and the interagency science consultation draft of the IRIS Toxicological Review of n-Butanol and the charge to external peer reviewers are posted on this site. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for n-butanol. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

Contemporary issues in toxicology the role of metabonomics in toxicology and its evaluation by the COMET project

International Nuclear Information System (INIS)

Lindon, John C.; Nicholson, Jeremy K.; Holmes, Elaine; Antti, Henrik; Bollard, Mary E.; Keun, Hector; Beckonert, Olaf; Ebbels, Timothy M.; Reily, Michael D.; Robertson, Donald; Stevens, Gregory J.; Luke, Peter; Breau, Alan P.; Cantor, Glenn H.; Bible, Roy H.; Niederhauser, Urs; Senn, Hans; Schlotterbeck, Goetz; Sidelmann, Ulla G.; Laursen, Steen M.; Tymiak, Adrienne; Car, Bruce D.; Lehman-McKeeman, Lois; Colet, Jean-Marie; Loukaci, Ali; Thomas, Craig

2003-01-01

The role that metabonomics has in the evaluation of xenobiotic toxicity studies is presented here together with a brief summary of published studies. To provide a comprehensive assessment of this approach, the Consortium for Metabonomic Toxicology (COMET) has been formed between six pharmaceutical companies and Imperial College of Science, Technology and Medicine (IC), London, UK. The objective of this group is to define methodologies and to apply metabonomic data generated using 1 H NMR spectroscopy of urine and blood serum for preclinical toxicological screening of candidate drugs. This is being achieved by generating databases of results for a wide range of model toxins which serve as the raw material for computer-based expert systems for toxicity prediction. The project progress on the generation of comprehensive metabonomic databases and multivariate statistical models for prediction of toxicity, initially for liver and kidney toxicity in the rat and mouse, is reported. Additionally, both the analytical and biological variation which might arise through the use of metabonomics has been evaluated. An evaluation of intersite NMR analytical reproducibility has revealed a high degree of robustness. Second, a detailed comparison has been made of the ability of the six companies to provide consistent urine and serum samples using a study of the toxicity of hydrazine at two doses in the male rat, this study showing a high degree of consistency between samples from the various companies in terms of spectral patterns and biochemical composition. Differences between samples from the various companies were small compared to the biochemical effects of the toxin. A metabonomic model has been constructed for urine from control rats, enabling identification of outlier samples and the metabolic reasons for the deviation. Building on this success, and with the completion of studies on approximately 80 model toxins, first expert systems for prediction of liver and kidney

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

Science.gov (United States)

2011-10-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Proposed National Toxicology... Session AGENCY: Division of the National Toxicology Program (DNTP), National Institute of Environmental.... Bucher, Associate Director, National Toxicology Program. [FR Doc. 2011-28132 Filed 10-28-11; 8:45 am...

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

Science.gov (United States)

2011-11-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Proposed National Toxicology Program (NTP) Review Process...: Division of the National Toxicology Program (DNTP), National Institute of Environmental Health Sciences.... Bucher, Associate Director, National Toxicology Program. [FR Doc. 2011-29615 Filed 11-15-11; 8:45 am...

Phytochemical Screening, Antibacterial and Toxicological Activities ...

African Journals Online (AJOL)

The phytochemical screening, antibacterial and toxicological activities of extracts of the stem bark of Acacia senegal were investigated. The phytochemical analyses according to standard screening tests using conventional protocols revealed the presence of tannins, saponins and sterols in the stem bark of the plant.

A medical-toxicological view of tattooing

DEFF Research Database (Denmark)

Laux, Peter; Tralau, Tewes; Tentschert, Jutta

2016-01-01

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...

FISH PHYSIOLOGY, TOXICOLOGY, AND WATER QUALITY

Science.gov (United States)

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...

A prospective toxicology analysis in alcoholics

DEFF Research Database (Denmark)

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

1997-01-01

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...

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

Energy Technology Data Exchange (ETDEWEB)

Templin-Branner, W.

2010-10-20

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

A case-based toxicology elective course to enhance student learning in pharmacotherapy.

Science.gov (United States)

Brown, Stacy D; Pond, Brooks B; Creekmore, Kathryn A

2011-08-10

To assess the impact of a case-based toxicology elective course on student learning in related required courses and student performance on the Pharmacy Curriculum Outcomes Assessment (PCOA) examination. A case-based clinical toxicology elective course that contained topics from 2 required courses, Pharmacology III and Pharmacotherapy II, was offered in the spring 2009 to second- and third-year pharmacy students. Scores on the Toxicology subsection of the PCOA of students enrolled in the elective were higher than those of students not enrolled (91.3% ± 4.1 vs. 67.2% ± 5.7). Enrollment in the elective was related to increased examination scores among Pharmacotherapy II students (89.5% ± 2.0 vs. 83.9% ± 1.8). Students indicated on course survey instruments that they were satisfied with the new elective offering. A toxicology elective provided a clinically relevant, active-learning experience for pharmacy students that addressed a curricular need within the college and increased examination scores.

76 FR 8741 - National Toxicology Program (NTP): Office of Liaison, Policy, and Review; Availability of Draft...

Science.gov (United States)

2011-02-15

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP): Office of Liaison... Materials The agenda topic is the peer review of the findings and conclusions of draft NTP TRs of toxicology... advisory committees. Dated: February 3, 2011. John R. Bucher, Associate Director, National Toxicology...

Liquid chromatography-mass spectrometry in forensic toxicology.

Science.gov (United States)

Van Bocxlaer, J F; Clauwaert, K M; Lambert, W E; Deforce, D L; Van den Eeckhout, E G; De Leenheer, A P

2000-01-01

Liquid chromatography-mass spectrometry has evolved from a topic of mainly research interest into a routinely usable tool in various application fields. With the advent of new ionization approaches, especially atmospheric pressure, the technique has established itself firmly in many areas of research. Although many applications prove that LC-MS is a valuable complementary analytical tool to GC-MS and has the potential to largely extend the application field of mass spectrometry to hitherto "MS-phobic" molecules, we must recognize that the use of LC-MS in forensic toxicology remains relatively rare. This rarity is all the more surprising because forensic toxicologists find themselves often confronted with the daunting task of actually searching for evidence materials on a scientific basis without any indication of the direction in which to search. Through the years, mass spectrometry, mainly in the GC-MS form, has gained a leading role in the way such quandaries are tackled. The advent of robust, bioanalytically compatible combinations of liquid chromatographic separation with mass spectrometric detection really opens new perspectives in terms of mass spectrometric identification of difficult molecules (e.g., polar metabolites) or biopolymers with toxicological relevance, high throughput, and versatility. Of course, analytical toxicologists are generally mass spectrometry users rather than mass spectrometrists, and this difference certainly explains the slow start of LC-MS in this field. Nevertheless, some valuable applications have been published, and it seems that the introduction of the more universal atmospheric pressure ionization interfaces really has boosted interests. This review presents an overview of what has been realized in forensic toxicological LC-MS. After a short introduction into LC-MS interfacing operational characteristics (or limitations), it covers applications that range from illicit drugs to often abused prescription medicines and some

Synthetic vitreous fibers: a review toxicology, epidemiology and regulations.

Science.gov (United States)

Bernstein, David M

2007-01-01

This review addresses the characteristics which differentiate synthetic vitreous fibers (SVFs, e.g., fiber glass, stonewool, slagwool, refractory ceramic fibers, etc.), how these influence the potential biopersistence and toxicity, the most recent epidemiological results and the integration of these findings into the health and safety regulations in Europe and the United States. Also presented is the historical basis for the European classification directive. The use and equivalence of the chronic inhalation toxicology and chronic intraperitoneal injection studies in laboratory rodents for evaluation of fiber toxicology is assessed as well as the impact of dose selection and design on the validity of the study. While synthetic vitreous fibers can span a wide range of chemistries, recognition and understanding of the importance of biopersistence (ability to persist in the lung) in fiber toxicity has led to the development of more and more biosoluble fibers (that break down rapidly in the lung). Still, the epidemiological data available which are largely based upon the use of fibers in past decades, indicate that the SVF do not present a human health risk at current exposure levels. The animal toxicology and biopersistence data provide a coherent basis for understanding and evaluating the parameters which affect SVF toxicity. The current regulations are based upon an extensive knowledge base of chronic studies in laboratory rodents which confirm the relationship between chronic adverse effects and the biopersistence of the longer fibers that can not be fully phagocytised and efficiently cleared from the lung. The amorphous structure of synthetic vitreous fibers facilitates designing fibers in use today with low biopersistence. Both the epidemiological data and the animal studies database provide strong assurance that there is little if any health risk associated with the use of SVFs of low biopersistence. IARC (2001) reclassified these fibers from Category 2b to

Ecotoxicity of silver nanomaterials in the aquatic environment: a review of literature and gaps in nano-toxicological research.

Science.gov (United States)

Walters, Chavon R; Pool, Edmund J; Somerset, Vernon S

2014-01-01

There has been extensive growth in nanoscale technology in the last few decades to such a degree that nanomaterials (NMs) have become a constituent in a wide range of commercial and domestic products. With NMs already in use in several consumer products, concerns have emerged regarding their potential adverse environmental impacts. Although research has been undertaken in order to minimise the gaps in our understanding of NMs in the environment, little is known about their bioavailability and toxicity in the aquatic environment. Nano-toxicology is defined as the study of the toxicity of nanomaterials. Nano-toxicology studies remain poorly and unevenly distributed. To date most of the research undertaken has been restricted to a narrow range of test species such as daphnids. Crabs are bio-indicators that can be used for toxicological research on NMs since they occupy a significant position in the aquatic food chain. In addition, they are often used in conventional ecotoxicological studies due to their high sensitivity to environmental stressors and are abundantly available. Because they are benthic organisms they are prone to contaminant uptake and bioaccumulation. To our knowledge the crab has never been used in nano-toxicological studies. In this context, an extensive review on published scientific literature on the ecotoxicity of silver NPs (AgNPs) on aquatic organisms was conducted. Some of the most common biomarkers used in ecotoxicological studies are described. Emphasis is placed on the use of biomarker responses in crabs as monitoring tools, as well as on its limitations. Additionally, the gaps in nano-toxicological research and recommendations for future research initiatives are addressed.

Toxicology of inorganic tin

International Nuclear Information System (INIS)

Burba, J.V.

1982-01-01

Tin(II) or stannous ion as a reducing agent is important in nuclear medicine because it is an essential component and common denominator for many in vivo radiodiagnostic agents, commonly called kits for the preparation of radiopharmaceuticals. This report is intended to alert nuclear medicine community regarding the wide range of biological effects that the stannous ion is capable of producing, and is a review of a large number of selected publications on the toxicological potential of tin(II)

Regulated necrosis and its implications in toxicology.

Science.gov (United States)

Aki, Toshihiko; Funakoshi, Takeshi; Uemura, Koichi

2015-07-03

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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

75 FR 26757 - National Toxicology Program (NTP); Office of Liaison, Policy and Review; Meeting of the...

Science.gov (United States)

2010-05-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP); Office of Liaison, Policy and Review; Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods... Director, National Toxicology Program. [FR Doc. 2010-11318 Filed 5-11-10; 8:45 am] BILLING CODE 4140-01-P ...

77 FR 72858 - Toxicological Review of Inorganic Arsenic (Cancer and Noncancer Effects): In Support of Summary...

Science.gov (United States)

2012-12-06

... public stakeholder workshop to inform the development of a state of the science toxicological review of... arsenic (iAs) public stakeholder workshop is designed to inform the planning for EPA's toxicological... impact the toxicological review, and discuss approaches for dose-response. The ultimate goals of the...

Initiation of a medical toxicology consult service at a tertiary care children's hospital.

Science.gov (United States)

Wang, George Sam; Monte, Andrew; Hatten, Benjamin; Brent, Jeffrey; Buchanan, Jennie; Heard, Kennon J

2015-05-01

Currently, only 10% of board-certified medical toxicologists are pediatricians. Yet over half of poison center calls involve children toxicology consultation is not common at children's hospitals. In collaboration with executive staff from Department of Pediatrics and Emergency Medicine, regional poison center, and our toxicology fellowship, we established a toxicology consulting service at our tertiary-care children's hospital. There were 139 consultations, and the service generated 13 consultations in the first month; median of 11 consultations per month thereafter (range 8-16). The service increased pediatric cases seen by the fellowship program from 30 to 94. The transition to a consult service required a culture change. Historically, call center advice was the mainstay of consulting practice and the medical staff was not accustomed to the availability of bedside medical toxicology consultations. However, after promotion of the service and full attending and fellowship coverage, consultations increased. In collaboration with toxicologists from different departments, a consultation service can be rapidly established. The service filled a clinical need that was disproportionately utilized for high acuity patients, immediately utilized by the medical staff and provided a robust pediatric population for the toxicology fellowship.

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

Energy Technology Data Exchange (ETDEWEB)

Templin-Branner, W.

2010-02-24

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

Cell-based in vitro models in environmental toxicology: a review

Directory of Open Access Journals (Sweden)

Poteser Michael

2017-10-01

Full Text Available An analysis of biological effects induced by environmental toxins and exposure-related evaluation of potential risks for health and environment represent central tasks in classical biomonitoring. While epidemiological data and population surveys are clearly the methodological frontline of this scientific field, cellbased in vitro assays provide information on toxin-affected cellular pathways and mechanisms, and are important sources for the identification of relevant biomarkers. This review provides an overview on currently available in vitro methods based on cultured cells, as well as some limitations and considerations that are of specific interest in the context of environmental toxicology. Today, a large number of different endpoints can be determined to pinpoint basal and specific toxicological cellular effects. Technological progress and increasingly refined protocols are extending the possibilities of cell-based in vitro assays in environmental toxicology and promoting their increasingly important role in biomonitoring.

Paradigm lost, paradigm found: The re-emergence of hormesis as a fundamental dose response model in the toxicological sciences

International Nuclear Information System (INIS)

Calabrese, Edward J.

2005-01-01

This paper provides an assessment of the toxicological basis of the hormetic dose-response relationship including issues relating to its reproducibility, frequency, and generalizability across biological models, endpoints measured and chemical class/physical stressors and implications for risk assessment. The quantitative features of the hormetic dose response are described and placed within toxicological context that considers study design, temporal assessment, mechanism, and experimental model/population heterogeneity. Particular emphasis is placed on an historical evaluation of why the field of toxicology rejected hormesis in favor of dose response models such as the threshold model for assessing non-carcinogens and linear no threshold (LNT) models for assessing carcinogens. The paper argues that such decisions were principally based on complex historical factors that emerged from the intense and protracted conflict between what is now called traditional medicine and homeopathy and the overly dominating influence of regulatory agencies on the toxicological intellectual agenda. Such regulatory agency influence emphasized hazard/risk assessment goals such as the derivation of no observed adverse effect levels (NOAELs) and the lowest observed adverse effect levels (LOAELs) which were derived principally from high dose studies using few doses, a feature which restricted perceptions and distorted judgments of several generations of toxicologists concerning the nature of the dose-response continuum. Such historical and technical blind spots lead the field of toxicology to not only reject an established dose-response model (hormesis), but also the model that was more common and fundamental than those that the field accepted. - The quantitative features of the hormetic dose/response are described and placed within the context of toxicology

Paradigm lost, paradigm found: The re-emergence of hormesis as a fundamental dose response model in the toxicological sciences

Energy Technology Data Exchange (ETDEWEB)

Calabrese, Edward J. [Environmental Health Sciences, School of Public Health, Morrill I, N344, University of Massachusetts, Amherst, MA 01003 (United States)]. E-mail: edwardc@schoolph.umass.edu

2005-12-15

This paper provides an assessment of the toxicological basis of the hormetic dose-response relationship including issues relating to its reproducibility, frequency, and generalizability across biological models, endpoints measured and chemical class/physical stressors and implications for risk assessment. The quantitative features of the hormetic dose response are described and placed within toxicological context that considers study design, temporal assessment, mechanism, and experimental model/population heterogeneity. Particular emphasis is placed on an historical evaluation of why the field of toxicology rejected hormesis in favor of dose response models such as the threshold model for assessing non-carcinogens and linear no threshold (LNT) models for assessing carcinogens. The paper argues that such decisions were principally based on complex historical factors that emerged from the intense and protracted conflict between what is now called traditional medicine and homeopathy and the overly dominating influence of regulatory agencies on the toxicological intellectual agenda. Such regulatory agency influence emphasized hazard/risk assessment goals such as the derivation of no observed adverse effect levels (NOAELs) and the lowest observed adverse effect levels (LOAELs) which were derived principally from high dose studies using few doses, a feature which restricted perceptions and distorted judgments of several generations of toxicologists concerning the nature of the dose-response continuum. Such historical and technical blind spots lead the field of toxicology to not only reject an established dose-response model (hormesis), but also the model that was more common and fundamental than those that the field accepted. - The quantitative features of the hormetic dose/response are described and placed within the context of toxicology.

75 FR 73085 - National Toxicology Program (NTP): Office of Liaison, Policy, and Review; Availability of Draft...

Science.gov (United States)

2010-11-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP): Office of Liaison... Materials The agenda topic is the peer review of the findings and conclusions of draft NTP TRs of toxicology.... Bucher, Associate Director, National Toxicology Program. [FR Doc. 2010-29945 Filed 11-26-10; 8:45 am...

Titanium dioxide: inhalation toxicology and epidemiology.

Science.gov (United States)

Hext, Paul M; Tomenson, John A; Thompson, Peter

2005-08-01

Titanium dioxide (TiO(2)) is manufactured worldwide in large quantities for use in a wide range of applications and is normally considered to be toxicologically inert. Findings of tumours in the lungs of rats exposed chronically to high concentrations of TiO(2), but not in similarly exposed mice or hamsters, suggest that the tumorigenic response may be a rat-specific phenomenon but nonetheless raises concerns for potential human health effects. With the limited toxicological understanding of species differences in response to inhaled TiO(2) and a similarly limited amount of epidemiological information with respect to TiO(2) exposure in the workplace, a consortium of TiO(2) manufacturers in Europe (under the European Chemistry Industry Council; CEFIC) and in North America (under the American Chemistry Council; ACC) initiated a programme of research to investigate inter-species differences as a result of exposure to TiO(2) and to conduct detailed epidemiological surveys of the major manufacturing sites. The toxicology studies exposed rats, mice and hamsters to pigment-grade TiO(2) (PG-TiO(2), 0, 10, 50 and 250 mg m(-3)) or ultrafine TiO(2) (UF-TiO(2), 0, 0.5, 2 and 10 mg m(-3)) for 90 days and the lung burdens and tissue responses were evaluated at the end of the exposure period and for up to 1 year after exposure. Results demonstrated clear species differences. Rats and mice had similar lung burdens and clearance rates while hamsters showed high clearance rates. At high lung particle burdens, rats showed a marked progression of histopathological lesions throughout the post-exposure period while mice and hamsters showed minimal initial lesions with recovery apparent during the post-exposure period. Lung neutrophil responses, a sensitive marker of inflammatory changes, reflected the development or recovery of the histopathological lesions. The use of surface area rather than gravimetric lung burden provided closer correlates of the burden to the biological effect

State-of-the-art of bone marrow analysis in forensic toxicology: a review.

Science.gov (United States)

Cartiser, Nathalie; Bévalot, Fabien; Fanton, Laurent; Gaillard, Yvan; Guitton, Jérôme

2011-03-01

Although blood is the reference medium in the field of forensic toxicology, alternative matrices are required in case of limited, unavailable or unusable blood samples. The present review investigated the suitability of bone marrow (BM) as an alternative matrix to characterize xenobiotic consumption and its influence on the occurrence of death. Basic data on BM physiology are reported in order to highlight the specificities of this matrix and their analytical and toxicokinetic consequences. A review of case reports, animal and human studies involving BM sample analysis focuses on the various parameters of interpretation of toxicological results: analytic limits, sampling location, pharmacokinetics, blood/BM concentration correlation, stability and postmortem redistribution. Tables summarizing the analytical conditions and quantification of 45 compounds from BM samples provide a useful tool for toxicologists. A specific section devoted to ethanol shows that, despite successful quantification, interpretation is highly dependent on postmortem interval. In conclusion, BM is an interesting alternative matrix, and further experimental data and validated assays are required to confirm its great potential relevance in forensic toxicology.

Pre-offense alcohol intake in homicide offenders and victims: A forensic-toxicological case-control study.

Science.gov (United States)

Hedlund, Jonatan; Forsman, Jonas; Sturup, Joakim; Masterman, Thomas

2018-05-01

Alcohol is associated with violent behavior, although little is known regarding to what extent alcohol increases homicide risk. We aimed to estimate risks of homicide offending and victimization conferred by the presence of ethanol in blood by using toxicological data from homicide victims and offenders and from controls who had died in vehicle-related accidents. From nationwide governmental registries and databases, forensic-toxicological results were retrieved for victims (n = 200) and offenders (n = 105) of homicides committed during the years 2007-2009 and individuals killed in vehicle-related accidents (n = 1629) during the years 2006-2014. Ethanol levels in blood exceeding 0.01 g/100 ml were considered positive. Using logistic regression, we found that the presence of ethanol in blood conferred a significantly increased risk of homicide offending (age-adjusted odds ratio [aOR] = 3.6, 95% confidence interval [95% CI] = 2.3-5.6) and homicide victimization (aOR = 2.1, 95% CI = 1.4-3.0). After stratification by sex, risk estimates in females were about 3-fold greater than in males for both homicide offending ([aOR = 11.0, 95% CI = 2.4-49.8] versus [aOR = 3.1, 95% CI = 1.9-4.9]) and victimization ([aOR = 5.4, 95% CI = 2.4-12.2] versus [aOR = 1.7, 95% CI = 1.1-2.8]). Sensitivity analyses yielded similar estimates. The results of the present study are consistent with prior findings suggesting alcohol to be an important risk factor for homicide offending and victimization. Surprisingly, however, associations were more pronounced in females, although additional studies that control for potential confounders are warranted to facilitate speculations about causality. Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Green Toxicology-Know Early About and Avoid Toxic Product Liabilities.

Science.gov (United States)

Maertens, Alexandra; Hartung, Thomas

2018-02-01

Toxicology uniquely among the life sciences relies largely on methods which are more than 40-years old. Over the last 3 decades with more or less success some additions to and few replacements in this toolbox took place, mainly as alternatives to animal testing. The acceptance of such new approaches faces the needs of formal validation and the conservative attitude toward change in safety assessments. Only recently, there is growing awareness that the same alternative methods, especially in silico and in vitro tools can also much earlier and before validation inform decision-taking in the product life cycle. As similar thoughts developed in the context of Green Chemistry, the term of Green Toxicology was coined to describe this change in approach. Here, the current developments in the alternative field, especially computational and more organo-typic cell cultures are reviewed, as they lend themselves to front-loaded chemical safety assessments. The initiatives of the Center for Alternatives to Animal Testing Green Toxicology Collaboration are presented. They aim first of all for forming a community to promote this concept and then for a cultural change in companies with the necessary training of chemists, product stewards and later regulators. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hair: a complementary source of bioanalytical information in forensic toxicology.

Science.gov (United States)

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

2011-01-01

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.

Novel strategies for sample preparation in forensic toxicology.

Science.gov (United States)

Samanidou, Victoria; Kovatsi, Leda; Fragou, Domniki; Rentifis, Konstantinos

2011-09-01

This paper provides a review of novel strategies for sample preparation in forensic toxicology. The review initially outlines the principle of each technique, followed by sections addressing each class of abused drugs separately. The novel strategies currently reviewed focus on the preparation of various biological samples for the subsequent determination of opiates, benzodiazepines, amphetamines, cocaine, hallucinogens, tricyclic antidepressants, antipsychotics and cannabinoids. According to our experience, these analytes are the most frequently responsible for intoxications in Greece. The applications of techniques such as disposable pipette extraction, microextraction by packed sorbent, matrix solid-phase dispersion, solid-phase microextraction, polymer monolith microextraction, stir bar sorptive extraction and others, which are rapidly gaining acceptance in the field of toxicology, are currently reviewed.

Evaluation of the Inhalation Toxicology Research Institute beagle dog closed breeding colony: a progress report

International Nuclear Information System (INIS)

Lustgarten, C.S.; Hobbs, C.H.; Muggenburg, B.A.; Benjamin, S.A.; Slauson, D.O.; Hahn, F.F.

1974-01-01

Since early 1968, a closed breeding colony has been in operation at the Inhalation Toxicology Research Institute to produce experimental dogs for inhalation toxicology studies and to replace colony breeding stock for producing dogs with a stable gene pool. From March 1, 1968 through July 15, 1974, 123 bitches were bred 613 times, resulting in 540 litters and 2809 puppies: a conception rate for this period of 88.9 percent. An average of 3.74 pups survived to one year of age. (U.S.)

Toxicologic evaluation of analytes from Tank 241-C-103

International Nuclear Information System (INIS)

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

1994-11-01

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

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.)

1980-09-01

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)

TOXNET and Beyond - Using the National Library of Medicine's Environmental Health and Toxicology Portal

International Nuclear Information System (INIS)

Templin-Branner, Wilma

2011-01-01

The purpose of this training is to familiarize participants with reliable online environmental health and toxicology information, from the National Library of Medicine and other reliable sources. Skills and knowledge acquired in this training class will enable participants to access, utilize, and refer others to environmental health and toxicology information. After completing this course, participants will be able to: (1) Identify quality, accurate, and authoritative online resources pertaining to environmental health, toxicology, and related medical information; (2) Demonstrate the ability to perform strategic search techniques to find relevant online information; and (3) Apply the skills and knowledge obtained in this class to their organization's health information needs. NLMs TOXNET (Toxicology Data Network) is a free, Web-based system of databases on toxicology, environmental health, hazardous chemicals, toxic releases, chemical nomenclatures, and specialty areas such as occupational health and consumer products. Types of information in the TOXNET databases include: (1) Specific chemicals, mixtures, and products; (2) Unknown chemicals; and (3) Special toxic effects of chemicals in humans and/or animals.

Data-intensive drug development in the information age: applications of Systems Biology/Pharmacology/Toxicology.

Science.gov (United States)

Kiyosawa, Naoki; Manabe, Sunao

2016-01-01

Pharmaceutical companies continuously face challenges to deliver new drugs with true medical value. R&D productivity of drug development projects depends on 1) the value of the drug concept and 2) data and in-depth knowledge that are used rationally to evaluate the drug concept's validity. A model-based data-intensive drug development approach is a key competitive factor used by innovative pharmaceutical companies to reduce information bias and rationally demonstrate the value of drug concepts. Owing to the accumulation of publicly available biomedical information, our understanding of the pathophysiological mechanisms of diseases has developed considerably; it is the basis for identifying the right drug target and creating a drug concept with true medical value. Our understanding of the pathophysiological mechanisms of disease animal models can also be improved; it can thus support rational extrapolation of animal experiment results to clinical settings. The Systems Biology approach, which leverages publicly available transcriptome data, is useful for these purposes. Furthermore, applying Systems Pharmacology enables dynamic simulation of drug responses, from which key research questions to be addressed in the subsequent studies can be adequately informed. Application of Systems Biology/Pharmacology to toxicology research, namely Systems Toxicology, should considerably improve the predictability of drug-induced toxicities in clinical situations that are difficult to predict from conventional preclinical toxicology studies. Systems Biology/Pharmacology/Toxicology models can be continuously improved using iterative learn-confirm processes throughout preclinical and clinical drug discovery and development processes. Successful implementation of data-intensive drug development approaches requires cultivation of an adequate R&D culture to appreciate this approach.

76 FR 8370 - National Toxicology Program (NTP); Office of Liaison, Policy and Review; Meeting of the NTP Board...

Science.gov (United States)

2011-02-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP); Office of Liaison... such as toxicology, pharmacology, pathology, biochemistry, epidemiology, risk assessment, carcinogenesis, mutagenesis, molecular biology, behavioral toxicology, neurotoxicology, immunotoxicology...

Arsenic in the groundwater: Occurrence, toxicological activities, and remedies.

Science.gov (United States)

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

2017-04-03

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.

IRIS Toxicological Review of Chloroform (Final Report)

Science.gov (United States)

EPA is announcing the release of the final report, Toxicological Review of Chloroform: in support of the Integrated Risk Information System (IRIS). The updated Summary for Chloroform and accompanying Quickview have also been added to the IRIS Database.

Identifying Key Events in AOPs for Embryonic Disruption using Computational Toxicology (European Teratology Society - AOP symp.)

Science.gov (United States)

Addressing safety aspects of drugs and environmental chemicals relies extensively on animal testing; however, the quantity of chemicals needing assessment and challenges of species extrapolation require alternative approaches to traditional animal studies. Newer in vitro and in s...

Systems Toxicology: The Future of Risk Assessment.

Science.gov (United States)

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

2015-01-01

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. © The Author(s) 2015.

FutureTox II: in vitro data and in silico models for predictive toxicology.

Science.gov (United States)

Knudsen, Thomas B; Keller, Douglas A; Sander, Miriam; Carney, Edward W; Doerrer, Nancy G; Eaton, David L; Fitzpatrick, Suzanne Compton; Hastings, Kenneth L; Mendrick, Donna L; Tice, Raymond R; Watkins, Paul B; Whelan, Maurice

2015-02-01

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 responses from in vitro and in silico data, and to define the goals for the future. Presentations and discussions were held on priority concerns such as predicting and modeling of metabolism, cell growth and differentiation, effects on sensitive subpopulations, and integrating data into risk assessment. Emerging trends in technologies such as stem cell-derived human cells, 3D organotypic culture models, mathematical modeling of cellular processes and morphogenesis, adverse outcome pathway development, and high-content imaging of in vivo systems were discussed. Although advances in moving towards an in vitro/in silico based risk assessment paradigm were apparent, knowledge gaps in these areas and limitations of technologies were identified. Specific recommendations were made for future directions and research needs in the areas of hepatotoxicity, cancer prediction, developmental toxicity, and regulatory toxicology. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Methods for the Compilation of a Core List of Journals in Toxicology.

Science.gov (United States)

Kuch, T. D. C.

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

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

Science.gov (United States)

2010-03-15

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Toxicology Program... authorities knowledgeable in fields such as toxicology, pharmacology, pathology, biochemistry, epidemiology, risk assessment, carcinogenesis, mutagenesis, molecular biology, behavioral toxicology, neurotoxicology...

Pharmacological toxicological studies on certain drugs subjected to radiation or used radioprotective agents

Energy Technology Data Exchange (ETDEWEB)

Hassan, S H.M. [Durng Research Dept., National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, (Egypt)

1995-10-01

The present study represents two main subjects. The first encounters the effect of radiosterilization of certain pharmaceretical preparations such as antihistaminics (cimetidine), anticonvulsants (diazepam), beta and calcium channel blacker (propranolol and verapamil) on their pharmacological activity. Results of this study revealed that the previously mentioned drugs can be effectively and safely sterilized by gamma irradiation without deleterious effect on their pharmacological activity. The other subject presented in this study is essentially a pharmacological subject encountering toxicological problems. Data of this study demonstrated that chemical radiation protection has been successfully reported using single drug administration has been successfully reported using single drug administration such as imidazole, and Sh-bearing compounds. In the present work, the radioprotective effect of imidazole was demonstrated on the cardiovascular and respiratory systems. Furthermore, combined drug administration was found to exert more protective action with less toxicity and therefore minimize the side effects of the radioprotective drugs. Thus, combination of imidazole and serotonin showed potential protective effect on blood gases was also reported. In addition, combination of cysteine and vitamin E afforded a better protection on adrenocortical function in rats than either agent alone. 4 figs., 1 tab.

Pharmacological toxicological studies on certain drugs subjected to radiation or used radioprotective agents

International Nuclear Information System (INIS)

Hassan, S.H.M.

1995-01-01

The present study represents two main subjects. The first encounters the effect of radiosterilization of certain pharmaceretical preparations such as antihistaminics (cimetidine), anticonvulsants (diazepam), beta and calcium channel blacker (propranolol and verapamil) on their pharmacological activity. Results of this study revealed that the previously mentioned drugs can be effectively and safely sterilized by gamma irradiation without deleterious effect on their pharmacological activity. The other subject presented in this study is essentially a pharmacological subject encountering toxicological problems. Data of this study demonstrated that chemical radiation protection has been successfully reported using single drug administration has been successfully reported using single drug administration such as imidazole, and Sh-bearing compounds. In the present work, the radioprotective effect of imidazole was demonstrated on the cardiovascular and respiratory systems. Furthermore, combined drug administration was found to exert more protective action with less toxicity and therefore minimize the side effects of the radioprotective drugs. Thus, combination of imidazole and serotonin showed potential protective effect on blood gases was also reported. In addition, combination of cysteine and vitamin E afforded a better protection on adrenocortical function in rats than either agent alone. 4 figs., 1 tab

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

DEFF Research Database (Denmark)

Grandjean, P

2015-01-01

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...... 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...... 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...

An analysis of a humidifier disinfectant case from a toxicological perspective

Directory of Open Access Journals (Sweden)

Kwangsik Park

2016-07-01

Full Text Available An analysis of patients and fatalities due to exposure to polyhexamethylene guanidine (PHMG shows that PHMG causes mainly lung diseases such as pulmonary fibrosis. However, no research on the other organs has been conducted on this matter yet. So, an in-depth discussion on toxicological techniques is needed to determine whether or not PHMG is toxic to organs other than just the lungs. For the test of target organ toxicity by PHMG exposure, a toxicokinetic study must first be conducted. However, measurement method for PHMG injected into the body has not yet been established because it is not easy to analyze polymer PHMG, so related base studies on analytical technique for PHMG including radio-labeling chemistry must come first. Moreover, research on exposure-biomarker and effect-biomarker must also be conducted, primarily related to clinical application. Several limitations seem to be expected to apply the biomarker study to the patient because much time has passed after exposure to the humidifier disinfectant. It is why a more comprehensive toxicological researches must be introduced to the causality for the victims.

An analysis of a humidifier disinfectant case from a toxicological perspective.

Science.gov (United States)

Park, Kawangsik

2016-01-01

An analysis of patients and fatalities due to exposure to polyhexamethylene guanidine (PHMG) shows that PHMG causes mainly lung diseases such as pulmonary fibrosis. However, no research on the other organs has been conducted on this matter yet. So, an in-depth discussion on toxicological techniques is needed to determine whether or not PHMG is toxic to organs other than just the lungs. For the test of target organ toxicity by PHMG exposure, a toxicokinetic study must first be conducted. However, measurement method for PHMG injected into the body has not yet been established because it is not easy to analyze polymer PHMG, so related base studies on analytical technique for PHMG including radio-labeling chemistry must come first. Moreover, research on exposure-biomarker and effect-biomarker must also be conducted, primarily related to clinical application. Several limitations seem to be expected to apply the biomarker study to the patient because much time has passed after exposure to the humidifier disinfectant. It is why a more comprehensive toxicological researches must be introduced to the causality for the victims.

Toxicological evaluation in silico and in vivo of secondary metabolites of Cissampelos sympodialis in Mus musculus mice following inhalation.

Science.gov (United States)

Alves, Mateus Feitosa; Ferreira, Larissa Adilis Maria Paiva; Gadelha, Francisco Allysson Assis Ferreira; Ferreira, Laércia Karla Diega Paiva; Felix, Mayara Barbalho; Scotti, Marcus Tullius; Scotti, Luciana; de Oliveira, Kardilândia Mendes; Dos Santos, Sócrates Golzio; Diniz, Margareth de Fátima Formiga Melo

2017-12-04

The ethanolic extract of the leaves of Cissampelos sympodialis showed great pharmacological potential, with inflammatory and immunomodulatory activities, however, it showed some toxicological effects. Therefore, this study aims to verify the toxicological potential of alkaloids of the genus Cissampelos through in silico methodologies, to develop a method in LC-MS/MS verifying the presence of alkaloids in the infusion and to evaluate the toxicity of the infusion of the leaves of C. sympodialis when inhaled by Swiss mice. Results in silico showed that alkaloid 93 presented high toxicological potential along with the products of its metabolism. LC-MS/MS results showed that the infusion of the leaves of this plant contained the alkaloids warifteine and methylwarifteine. Finally, the in vivo toxicological analysis of the C. sympodialis infusion showed results, both in biochemistry, organ weights and histological analysis, that the infusion of C. sympodialis leaves presents a low toxicity.

Phytochemical analysis and toxicological evaluation of the ...

African Journals Online (AJOL)

Phytochemical analysis revealed the presence of tannins, Flavonoid, Alkaloids, Anthraquinone, Saponin and Cardiac glycosides. This work thus justifies the ethnomedicinal use of the plant in the treatment of anaemia and its safety profile. Keywords: Toxicological, Ethno toxicity, Hematological and phytochemical ...

77 FR 40358 - Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM)

Science.gov (United States)

2012-07-09

..., revised, and alternative safety testing methods with regulatory applicability and promotes the scientific... DEPARTMENT OF HEALTH AND HUMAN SERVICES Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) AGENCY: Division of the National Toxicology Program (DNTP...

Pharmacokinetics and expert systems as aids for risk assessment in reproductive toxicology.

OpenAIRE

Mattison, D R; Jelovsek, F R

1987-01-01

A minimal approach to risk assessment in reproductive toxicology involves four components: hazard identification, hazard characterization, exposure characterization, and risk characterization. In practice, risk assessment in reproductive toxicology has been reduced to arbitrary safety factors or mathematical models of the dose-response relationship. These approaches obscure biological differences across species rather than using this important and frequently accessible information. Two approa...

Integration of clinical chemistry, expression, and metabolite data leads to better toxicological class separation

DEFF Research Database (Denmark)

Spicker, Jeppe; Brunak, Søren; Frederiksen, K.S.

2008-01-01

A large number of databases are currently being implemented within toxicology aiming to integrate diverse biological data, such as clinical chemistry, expression, and other types of data. However, for these endeavors to be successful, tools for integration, visualization, and interpretation...... are needed. This paper presents a method for data integration using a hierarchical model based on either principal component analysis or partial least squares discriminant analysis of clinical chemistry, expression, and nuclear magnetic resonance data using a toxicological study as case. The study includes...... the three toxicants alpha-naphthyl-isothiocyanate, dimethylnitrosamine, and N-methylformamide administered to rats. Improved predictive ability of the different classes is seen, suggesting that this approach is a suitable method for data integration and visualization of biological data. Furthermore...

Status of characterization techniques for carbon nanotubes and suggestions towards standards suitable for toxicological assessment

International Nuclear Information System (INIS)

Schweinberger, Florian F; Meyer-Plath, Asmus

2011-01-01

Nanotechnologies promise to contribute significantly to major technological challenges of the upcoming century. Despite profound scientific progress in the last decades, only minor advances have been made in the field of nanomaterial toxicology. The International Team in Nanosafety (TITNT) is an international and multidisciplinary group of scientists, which aims at better understanding the risks of nanomaterials. Carbon nanotubes (CNT) account for one of the most promising nanomaterials and have therefore been chosen as representative material for nanoscaled particles. They are currently investigated by the different platforms of TITNT. As a starting point, the present report summarizes a literature-based study on the physico-chemical properties of CNT, as they are closely linked with toxicological properties. A brief introduction to synthesis, purification and material properties is given. Characterization methods for CNT are discussed with respect to their reliability and the information content on chemical properties. Recommendations for a set of standard characterizations mandatory for toxicological assessment are derived.

Status of characterization techniques for carbon nanotubes and suggestions towards standards suitable for toxicological assessment

Science.gov (United States)

Schweinberger, Florian F.; Meyer-Plath, Asmus

2011-07-01

Nanotechnologies promise to contribute significantly to major technological challenges of the upcoming century. Despite profound scientific progress in the last decades, only minor advances have been made in the field of nanomaterial toxicology. The International Team in Nanosafety (TITNT) is an international and multidisciplinary group of scientists, which aims at better understanding the risks of nanomaterials. Carbon nanotubes (CNT) account for one of the most promising nanomaterials and have therefore been chosen as representative material for nanoscaled particles. They are currently investigated by the different platforms of TITNT. As a starting point, the present report summarizes a literature-based study on the physico-chemical properties of CNT, as they are closely linked with toxicological properties. A brief introduction to synthesis, purification and material properties is given. Characterization methods for CNT are discussed with respect to their reliability and the information content on chemical properties. Recommendations for a set of standard characterizations mandatory for toxicological assessment are derived.

Status of characterization techniques for carbon nanotubes and suggestions towards standards suitable for toxicological assessment

Energy Technology Data Exchange (ETDEWEB)

Schweinberger, Florian F, E-mail: florian.schweinberger@tum.de [International Team in Nanosafety (TITNT) and Technische Universitaet Muenchen, Catalysis Research Center, Chair of Physical Chemistry, Lichtenbergstr. 4, 85748 Garching (Germany); Meyer-Plath, Asmus [International Team in Nanosafety (TITNT) and BAM - Federal Institute for Materials Research and Testing, Division VI.5 - Polymer Surfaces, Unter den Eichen 87, 12205 Berlin (Germany)

2011-07-06

Nanotechnologies promise to contribute significantly to major technological challenges of the upcoming century. Despite profound scientific progress in the last decades, only minor advances have been made in the field of nanomaterial toxicology. The International Team in Nanosafety (TITNT) is an international and multidisciplinary group of scientists, which aims at better understanding the risks of nanomaterials. Carbon nanotubes (CNT) account for one of the most promising nanomaterials and have therefore been chosen as representative material for nanoscaled particles. They are currently investigated by the different platforms of TITNT. As a starting point, the present report summarizes a literature-based study on the physico-chemical properties of CNT, as they are closely linked with toxicological properties. A brief introduction to synthesis, purification and material properties is given. Characterization methods for CNT are discussed with respect to their reliability and the information content on chemical properties. Recommendations for a set of standard characterizations mandatory for toxicological assessment are derived.

Toxicological studies on irradiated food and food constituents

International Nuclear Information System (INIS)

Schubert, J.

1978-01-01

Selected aspects of the genotoxicology and chemistry of irradiated foods and food components are critically examined and compared with other food processing operations such as cooking, and intentional use of food additives. For example, it is estimated that if 10% of an average daily diet contained irradiated (<1.0Mrad) foods, the daily consumption of radiolytic products would be 2-20mg/d compared with a total of approximately 4000mg/d of intentional food additives and approximately 80mg/d of toxic inorganic and organic environmentally derived contaminants. Several recommendations for the genotoxicological testing of irradiated foods are given, including: (1) that feeding tests include a control diet consisting of food processed by one of the standard methods such as thermalization; (2) that more use be made of positive controls so as to have a 'built-in' measure of sensitivity and responsiveness; (3) that a battery of in vitro and in vivo short-term mutagenicity tests be performed prior to the carrying out of the long-term feeding tests; and (4) that an irradiated food be tested after it is cooked in the manner normally consumed, which may, of course, include the raw or uncooked state as well. An outline of current genetic-toxicological testing schemes is provided and examined. Emphasis is given to a modification in the protocols for the Ames mutagenicity tests leading to a reduction in the evidence of false positives and false negatives. Also described is a procedure for systematically studying combined or interactive effects, acute or chronic, which requires no more effort than that needed for testing a single agent and which yields complete dose-response curves. It is concluded that food irradiation, as a physical process, appears more advantageous from the genotoxicological, chemical, and pollution aspects than well-accepted, but actually rarely tested, physical processes such as canning. (author)

A global epidemiological perspective on the toxicology of drug-facilitated sexual assault: A systematic review.

Science.gov (United States)

Anderson, Laura Jane; Flynn, Asher; Pilgrim, Jennifer Lucinda

2017-04-01

A systematic review was undertaken to determine the current global prevalence of drug-facilitated sexual assault (DFSA) reported in adults in order to identify trends in the toxicology findings in DFSA around the world over the past 20 years. Databases PubMed, PsycINFO and Scopus were systematically searched using the terms: "drug-facilitated sexual assault", "chemical submission", "date rape", "rape drugs" and "drink-spiking" to identify relevant studies for inclusion in the review. This study focused on adult victims of suspected DFSA aged 16 years and above in which toxicology results were reported. The majority of studies included were published in the United States, followed by the United Kingdom, with only a single study dedicated to this area in both Australia and Europe. Epidemiology, prevalence rates, and toxicology for DFSA appear broadly commensurate across different continents, although there are some differences in how "drug-facilitated sexual assault" is defined, as well as differences in the sensitivity of toxicological analyses. Nonetheless, alcohol is the most commonly detected substance and co-occurrence with other drugs is common. Aside from alcohol there was no other specific drug category associated with DFSA. Cannabinoids and benzodiazepines were frequently detected, but a lack of contextual information made it difficult to establish the extent that these substances contributed to suspected cases of DFSA. This comprehensive review suggests that alcohol intoxication combined with voluntary drug consumption presents the greatest risk factor for DFSA, despite populist perceptions that covert drink-spiking is a common occurrence. There is a need to develop policies that encourage early responders to suspected DFSA (e.g., law enforcement agencies, medical staff, support agencies, etc), to collect detailed information about the individual's licit and illicit drug consumption history, in order to assist in providing appropriate and more thorough

Using energy budgets to combine ecology and toxicology in a mammalian sentinel species

Science.gov (United States)

Desforges, Jean-Pierre W.; Sonne, Christian; Dietz, Rune

2017-04-01

Process-driven modelling approaches can resolve many of the shortcomings of traditional descriptive and non-mechanistic toxicology. We developed a simple dynamic energy budget (DEB) model for the mink (Mustela vison), a sentinel species in mammalian toxicology, which coupled animal physiology, ecology and toxicology, in order to mechanistically investigate the accumulation and adverse effects of lifelong dietary exposure to persistent environmental toxicants, most notably polychlorinated biphenyls (PCBs). Our novel mammalian DEB model accurately predicted, based on energy allocations to the interconnected metabolic processes of growth, development, maintenance and reproduction, lifelong patterns in mink growth, reproductive performance and dietary accumulation of PCBs as reported in the literature. Our model results were consistent with empirical data from captive and free-ranging studies in mink and other wildlife and suggest that PCB exposure can have significant population-level impacts resulting from targeted effects on fetal toxicity, kit mortality and growth and development. Our approach provides a simple and cross-species framework to explore the mechanistic interactions of physiological processes and ecotoxicology, thus allowing for a deeper understanding and interpretation of stressor-induced adverse effects at all levels of biological organization.

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

Science.gov (United States)

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

Depleted and natural uranium: chemistry and toxicological effects.

Science.gov (United States)

Craft, Elena; Abu-Qare, Aquel; Flaherty, Meghan; Garofolo, Melissa; Rincavage, Heather; Abou-Donia, Mohamed

2004-01-01

Depleted uranium (DU) is a by-product from the chemical enrichment of naturally occurring uranium. Natural uranium is comprised of three radioactive isotopes: (238)U, (235)U, and (234)U. This enrichment process reduces the radioactivity of DU to roughly 30% of that of natural uranium. Nonmilitary uses of DU include counterweights in airplanes, shields against radiation in medical radiotherapy units and transport of radioactive isotopes. DU has also been used during wartime in heavy tank armor, armor-piercing bullets, and missiles, due to its desirable chemical properties coupled with its decreased radioactivity. DU weapons are used unreservedly by the armed forces. Chemically and toxicologically, DU behaves similarly to natural uranium metal. Although the effects of DU on human health are not easily discerned, they may be produced by both its chemical and radiological properties. DU can be toxic to many bodily systems, as presented in this review. Most importantly, normal functioning of the kidney, brain, liver, and heart can be affected by DU exposure. Numerous other systems can also be affected by DU exposure, and these are also reviewed. Despite the prevalence of DU usage in many applications, limited data exist regarding the toxicological consequences on human health. This review focuses on the chemistry, pharmacokinetics, and toxicological effects of depleted and natural uranium on several systems in the mammalian body. A section on risk assessment concludes the review.

Toxicology of plutonium

International Nuclear Information System (INIS)

Bair, W.J.

1974-01-01

Data are reviewed from studies on the toxicity of Pu in experimental animals. Of the several plutonium isotopes, only 238 Pu and 239 Pu have been studied well. Sufficient results have been obtained to show that the behavior of 238 Pu in biological systems and the resulting biological effects cannot be precisely predicted from studies of 239 Pu. This probably applies also to other radiologically important plutonium isotopes which have half-lives ranging from 45 days to 10 7 years and decay by β-emission, electron capture, and spontaneous fission, as well as by emission of α-particles. All the biological effects of plutonium described in this review are attributed to alpha-particle radiation emitted by the plutonium. However, since plutonium is a chemically active heavy metal, one cannot ignore the possibility of chemical toxicity of the low-specific-activity isotopes, 239 Pu, 242 Pu, and 244 Pu. The preponderance of our knowledge of plutonium toxicology has come from short-term studies of relatively high dosage levels in several animal species. The consequences of high-level internal exposures can be predicted with confidence in experimental animals and probably also in man. However, considering the care with which plutonium is handled in the nuclear industry, a high-level contamination event is unlikely. Considerably less is known about the long-term effects of low levels of contamination. (250 references) (U.S.)

Behavioral teratologic studies using microwave radiation: is there an increased risk from exposure to cellular phones and microwave ovens?

Science.gov (United States)

Jensh, R P

1997-01-01

The objective of the investigations presented in this review was to determine if there are adverse effects due to chronic prenatal microwave exposure in rats at term and/or alterations in neonatal and adult offspring psychophysiologic development and growth. Following the establishment of a nonhyperthermal power density level of microwave radiation, pregnant rats were exposed throughout pregnancy to continuous wave 915 MHz, 2450 MHz, or 6000 MHz radiation at power density levels of 10, 20, or 35 mW/cm2, respectively. Teratologic evaluation included the following parameters: maternal weight and weight gain; mean litter size; maternal organ weight and organ weight/body weight ratios; body weight ratios of brain, liver, kidneys, and ovaries; maternal peripheral blood parameters including hematocrit, hemoglobin, and white cell counts; number of resorptions and resorption rate; number of abnormalities and abnormality rate; mean term fetal weight. Mothers were rebred, and the second, nonexposed litters were evaluated for teratogenic effects. Exposed offspring were evaluated using the following perinatal and adult tests: eye opening, surface righting, negative geotaxis, auditory startle, air righting, open field, activity wheel, swimming, and forelimb hanging. Offspring were also monitored for weekly weight and weight gain. Animals exposed to 915 MHz did not exhibit any consistent significant alterations in any of the above parameters. Exposure to 2450 MHz resulted only in a significantly increased adult offspring activity level compared to nonexposed offspring. Offspring exposed to 6000 MHz radiation exhibited an initial slight, but significant, retardation in term weight, while mothers had a significantly reduced monocyte count. No changes in any of the other term parameters were observed. A few postnatal parameters were affected in offspring exposed to 6000 MHz. Weekly weights were lower in the exposed offspring, but they recovered by the fifth week. Eye opening was

In vitro toxicological characterization of particulate emissions from residential biomass heating systems based on old and new technologies

Science.gov (United States)

Jalava, Pasi I.; Happo, Mikko S.; Kelz, Joachim; Brunner, Thomas; Hakulinen, Pasi; Mäki-Paakkanen, Jorma; Hukkanen, Annika; Jokiniemi, Jorma; Obernberger, Ingwald; Hirvonen, Maija-Riitta

2012-04-01

Residential wood combustion causes major effects on the air quality on a global scale. The ambient particulate levels are known to be responsible for severe adverse health effects that include e.g. cardio-respiratory illnesses and cancer related effects, even mortality. It is known that biomass combustion derived emissions are affected by combustion technology, fuel being used and user-related practices. There are also indications that the health related toxicological effects are influenced by these parameters. This study we evaluated toxicological effects of particulate emissions (PM1) from seven different residential wood combusting furnaces. Two appliances i.e. log wood boiler and stove represented old batch combustion technology, whereas stove and tiled stove were designated as new batch combustion as three modern automated boilers were a log wood boiler, a woodchip boiler and a pellet boiler. The PM1 samples from the furnaces were collected in an experimental setup with a Dekati® gravimetric impactor on PTFE filters with the samples being weighed and extracted from the substrates and prior to toxicological analyses. The toxicological analyses were conducted after a 24-hour exposure of the mouse RAW 264.7 macrophage cell line to four doses of emission particle samples and analysis of levels of the proinflammatory cytokine TNFα, chemokine MIP-2, cytotoxicity with three different methods (MTT, PI, cell cycle analysis) and genotoxicity with the comet assay. In the correlation analysis all the toxicological results were compared with the chemical composition of the samples. All the samples induced dose-dependent increases in the studied parameters. Combustion technology greatly affected the emissions and the concomitant toxicological responses. The modern automated boilers were usually the least potent inducers of most of the parameters while emissions from the old technology log wood boiler were the most potent. In correlation analysis, the PAH and other organic

Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) in toxicological analysis. Studies on the detection of clobenzorex and its metabolites within a systematic toxicological analysis procedure by GC-MS and by immunoassay and studies on the detection of alpha- and beta-amanitin in urine by atmospheric pressure ionization electrospray LC-MS.

Science.gov (United States)

Maurer, H H; Kraemer, T; Ledvinka, O; Schmitt, C J; Weber, A A

1997-02-07

GC-MS is the method of choice for toxicological analysis of toxicants volatile in GC while non-volatile and/or thermally labile toxicants need LC-MS for their determination. Studies are presented on the toxicological detection of the amphetamine-like anorectic clobenzorex in urine by GC-MS after acid hydrolysis, extraction and acetylation and by fluorescence polarization immunoassay (FPIA, TDx (meth)amphetamine II). After ingestion of 60 mg of clobenzorex, the parent compound and/or its metabolites could be detected by GC-MS for up to 84 h or by FPIA for up to 60 h. Since clobenzorex shows no cross-reactivity with the used immunoassay, the N-dealkylated metabolite amphetamine is responsible for the positive TDx results. The intake of clobenzorex instead of amphetamine can be differentiated by GC-MS detection of hydroxyclobenzorex which is detectable for at least as long as amphetamine. In addition, the described GC-MS procedure allows the simultaneous detection of most of the toxicologically relevant drugs. Furthermore, studies are described on the atmospheric pressure ionization electrospray LC-MS detection of alpha- and beta-amanitin, toxic peptides of amanita mushrooms, in urine after solid-phase extraction on RP-18 columns. Using the single ion monitoring mode with the ions m/z 919 and 920 the amanitins could be detected down to 10 ng/ml of urine which allows us to diagnose intoxications with amanita mushrooms.

Authentication of synthetic environmental contaminants and their (bio)transformation products in toxicology: polychlorinated biphenyls as an example.

Science.gov (United States)

Li, Xueshu; Holland, Erika B; Feng, Wei; Zheng, Jing; Dong, Yao; Pessah, Isaac N; Duffel, Michael W; Robertson, Larry W; Lehmler, Hans-Joachim

2018-01-10

Toxicological studies use "specialty chemicals" and, thus, should assess and report both identity and degree of purity (homogeneity) of the chemicals (or toxicants) under investigation to ensure that other scientists can replicate experimental results. Although detailed reporting criteria for the synthesis and characterization of organic compounds have been established by organic chemistry journals, such criteria are inconsistently applied to the chemicals used in toxicological studies. Biologically active trace impurities may lead to incorrect conclusions about the chemical entity responsible for a biological response, which in turn may confound risk assessment. Based on our experience with the synthesis of PCBs and their metabolites, we herein propose guidelines for the "authentication" of synthetic PCBs and, by extension, other organic toxicants, and provide a checklist for documenting the authentication of toxicants reported in the peer-reviewed literature. The objective is to expand guidelines proposed for different types of biomedical and preclinical studies to include a thorough authentication of specialty chemicals, such as PCBs and their derivatives, with the goal of ensuring transparent and open reporting of scientific results in toxicology and the environmental health sciences.

Multiscale Toxicology- Building the Next Generation Tools for Toxicology

Energy Technology Data Exchange (ETDEWEB)

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

2013-10-31

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

Testing of Binders Toxicological Effects

Science.gov (United States)

Strokova, V.; Nelyubova, V.; Rykunova, M.

2017-11-01

The article presents the results of a study of the toxicological effect of binders with different compositions on the vital activity of plant and animal test-objects. The analysis of the effect on plant cultures was made on the basis of the phytotesting data. The study of the effect of binders on objects of animal origin was carried out using the method of short-term testing. Based on the data obtained, binders are ranked according to the degree of increase in the toxic effect: Gypsum → Portland cement → Slag Portland cement. Regardless of the test-object type, the influence of binders is due to the release of various elements (calcium ions or heavy metals) into the solution. In case of plant cultures, the saturation of the solution with elements has a positive effect (there is no inhibitory effect), and in case of animal specimens - an increase in the toxic effect.

Process in Developing Zebra fish Laboratory at Malaysian Nuclear Agency for Toxicology Studies

International Nuclear Information System (INIS)

Fazliana Mohd Saaya; Mohd Noor Hidayat Adenan; Anee Suryani Sued