Mercury Toxicity

Total Page:16

File Type:pdf, Size:1020Kb

Mercury Toxicity Journal of Biomedicine and Biotechnology Mercury Toxicity Guest Editors: João B. T. Rocha, Michael Aschner, José G. Dórea, Sandra Ceccatelli, Marcelo Farina, and Luiz Carlos L. Silveira Mercury Toxicity Journal of Biomedicine and Biotechnology Mercury Toxicity Guest Editors: Joao˜ B. T. Rocha, Michael Aschner, JoseG.D´ orea,´ Sandra Ceccatelli, Marcelo Farina, and Luiz Carlos L. Silveira Copyright © 2012 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in “Journal of Biomedicine and Biotechnology.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board The editorial board of the journal is organized into sections that correspond to the subject areas covered by the journal. Agricultural Biotechnology Ahmad Zuhairi Abdullah, Malaysia Hari B. Krishnan, USA B. C. Saha, USA Guihua H. Bai, USA Carol A. Mallory-Smith, USA Abdurrahman Saydut, Turkey Christopher P. Chanway, Canada Xiaoling Miao, China Mariam B. Sticklen, USA Ravindra N. Chibbar, Canada Dennis P. Murr, Canada Kok Tat Tan, Malaysia Adriana S. Franca, Brazil Rodomiro Ortiz, Sweden Chiu-Chung Young, Taiwan Ian Godwin, Australia Encarnacion´ Ruiz, Spain Animal Biotechnology E. S. Chang, USA Tosso Leeb, Switzerland Lawrence B. Schook, USA Bhanu P. Chowdhary, USA James D. Murray, USA Mari A. Smits, The Netherlands Noelle E. Cockett, USA Anita M. Oberbauer, USA Leon Spicer, USA Peter Dovc, Slovenia Jorge A. Piedrahita, USA J. Verstegen, USA Scott C. Fahrenkrug, USA Daniel Pomp, USA Matthew B. Wheeler, USA Dorian J. Garrick, USA Kent M. Reed, USA Kenneth L. White, USA Thomas A. Hoagland, USA Lawrence Reynolds, USA Biochemistry David Ronald Brown, UK Hicham Fenniri, Canada Wen-HwaLee,USA Saulius Butenas, USA Nick V. Grishin, USA George Makhatadze, USA Vittorio Calabrese, Italy J. Guy Guillemette, Canada Leonid Medved, USA Miguel Castanho, Portugal Paul W. Huber, USA Susan A. Rotenberg, USA Francis J. Castellino, USA Chen-Hsiung Hung, Taiwan Jason Shearer, USA Roberta Chiaraluce, Italy MariaJerzykiewicz,Poland Andrei Surguchov, USA D. M. Clarke, Canada Michael Kalafatis, USA John B. Vincent, USA Francesca Cutruzzola,` Italy B. E. Kemp, Australia Y. George Zheng, USA Paul W. Doetsch, USA Phillip E. Klebba, USA Bioinformatics T. Akutsu, Japan Eugenio´ Ferreira, Portugal Zoran Obradovic, USA Miguel A. Andrade, Germany Stavros J. Hamodrakas, Greece Florencio Pazos, Spain Mark Y. Borodovsky, USA Paul Harrison, USA Zhirong Sun, China Rita Casadio, Italy George Karypis, USA Ying Xu, USA David Corne, UK Guohui Lin, Canada Alexander Zelikovsky, USA Sorin Draghici, USA Satoru Miyano, Japan Albert Zomaya, Australia Biophysics Miguel Castanho, Portugal Ali A. Khraibi, Saudi Arabia S. B. Petersen, Denmark P. Bryant Chase, USA Rumiana Koynova, USA Peter Schuck, USA Kuo-Chen Chou, USA Serdar Kuyucak, Australia Claudio M. Soares, Portugal Rizwan Khan, India Jianjie Ma, USA Cell Biology Omar Benzakour, France Xudong Huang, USA Michael Sheetz, USA Sanford I. Bernstein, USA Anton M. Jetten, USA JamesL.Sherley,USA Phillip I. Bird, Australia Seamus J. Martin, Ireland G. S. Stein, USA Eric Bouhassira, USA Manuela Martins-Green, USA Richard Tucker, USA Mohamed Boutjdir, USA Shoichiro Ono, USA Thomas van Groen, USA Chung-Liang Chien, Taiwan George Perry, USA Andre Van Wijnen, USA Richard Gomer, USA M. Piacentini, Italy Steve Winder, UK Paul J. Higgins, USA George E. Plopper, USA Chuanyue Wu, USA Pavel Hozak, Czech Republic Lawrence Rothblum, USA Bin-Xian Zhang, USA Genetics Adewale Adeyinka, USA J. Spencer Johnston, USA Raj S. Ramesar, South Africa Claude Bagnis, France M. Ilyas Kamboh, USA Elliot D. Rosen, USA J. Birchler, USA Feige Kaplan, Canada Dharambir K. Sanghera, USA Susan Blanton, USA Manfred Kayser, The Netherlands Michael Schmid, Germany BarryJ.Byrne,USA Brynn Levy, USA Markus Schuelke, Germany R. Chakraborty, USA Xiao Jiang Li, USA Wolfgang Arthur Schulz, Germany Domenico Coviello, Italy Thomas Liehr, Germany Jorge Sequeiros, Portugal Sarah H. Elsea, USA JamesM.Mason,USA Mouldy Sioud, Norway Celina Janion, Poland Mohammed Rachidi, France Rongjia Zhou, China Genomics Vladimir Bajic, Saudi Arabia J. Spencer Johnston, USA John V. Moran, USA Margit Burmeister, USA Vladimir Larionov, USA Yasushi Okazaki, Japan Settara Chandrasekharappa, USA Thomas Lufkin, Singapore Gopi K. Podila, USA Yataro Daigo, Japan John L. McGregor, France Momiao Xiong, USA Immunology Hassan Alizadeh, USA James D. Gorham, USA Kanury V. S. Rao, India Peter Bretscher, Canada Silvia Gregori, Italy Yair Reisner, Israel Robert E. Cone, USA Thomas Griffith, USA HarryW.Schroeder,USA Terry L. Delovitch, Canada Young S. Hahn, USA Wilhelm Schwaeble, UK Anthony L. DeVico, USA DorothyE.Lewis,USA Nilabh Shastri, USA Nick Di Girolamo, Australia Bradley W. McIntyre, USA Yufang Shi, China Don Mark Estes, USA R. Lee Mosley, USA Piet Stinissen, Belgium Soldano Ferrone, USA Marija Mostarica-Stojkovic,´ Serbia Hannes Stockinger, Austria Jeffrey A. Frelinger, USA Hans Konrad Muller, Australia Graham R. Wallace, UK John Robert Gordon, Canada Ali Ouaissi, France Microbial Biotechnology Suraini Abd-Aziz, Malaysia Peter Coloe, Australia Paula Loureiro Paulo, Brazil Jozef Anne,´ Belgium Daniele Daffonchio, Italy Bernd H A Rehm, New Zealand Nuri Azbar, Turkey Han de Winde, The Netherlands Alberto Reis, Portugal Yoav Bashan, Mexico Raf Dewil, Belgium Muthuswamy Sathishkumar, Singapore Marco Bazzicalupo, Italy Jos Domingos Fontana, Brazil Ramkrishna Sen, India Hakan Bermek, Turkey Petros Gikas, Greece Angela Sessitsch, Austria Nico Boon, Belgium Tom Granstrom, Finland Ya-Jie Tang, China JoseLuisCampos,Spain´ Ismail Kiran, Turkey Orhan Yenigun, Turkey Yinguang Chen, China Hongjuan Liu, China Eileen Hao Yu, UK Luca Simone Cocolin, Italy Yanhe Ma, China Microbiology D. Beighton, UK Gad Frankel, UK Didier A. Raoult, France Steven R. Blanke, USA Roy Gross, Germany Isabel Sa-Correia,´ Portugal Stanley Brul, The Netherlands Hans-Peter Klenk, Germany P. L. C. Small, USA IsaacK.O.Cann,USA Tanya Parish, UK Michael Thomm, Germany Stephen K. Farrand, USA Gopi K. Podila, USA H. C. van der Mei, The Netherlands Alain Filloux, UK Frederick D. Quinn, USA Schwan William, USA Molecular Biology Rudi Beyaert, Belgium David W. Litchfield, Canada Elena Orlova, UK Michael Bustin, USA Wuyuan Lu, USA Yeon-Kyun Shin, USA Douglas Cyr, USA Patrick Matthias, Switzerland William S. Trimble, Canada K. Iatrou, Greece John L. McGregor, France Lisa Wiesmuller, Germany Lokesh Joshi, Ireland S. L. Mowbray, Sweden Masamitsu Yamaguchi, Japan Oncology Colin Cooper, UK Daehee Kang, Republic of Korea Frank Pajonk, USA F. M. J. Debruyne, The Netherlands Abdul R. Khokhar, USA Waldemar Priebe, USA Nathan Ames Ellis, USA Rakesh Kumar, USA F. C. Schmitt, Portugal Dominic Fan, USA Macus Tien Kuo, USA Sonshin Takao, Japan Gary E. Gallick, USA Eric W. Lam, UK Ana Maria Tari, USA DailaS.Gridley,USA Sue-Hwa Lin, USA Henk G. Van Der Poel, The Netherlands Xin-yuan Guan, Hong Kong Kapil Mehta, USA Haodong Xu, USA Anne Hamburger, USA Orhan Nalcioglu, USA David J. Yang, USA Manoor Prakash Hande, Singapore P. J. Oefner, Germany Beric Henderson, Australia Allal Ouhtit, Oman Pharmacology Abdel A. Abdel-Rahman, USA Ayman El-Kadi, Canada Kennerly S. Patrick, USA M. Badr, USA Jeffrey Hughes, USA Vickram Ramkumar, USA Stelvio M. Bandiera, Canada Kazim Husain, USA Michael J. Spinella, USA Ronald E. Baynes, USA Farhad Kamali, UK Quadiri Timour, France R. Keith Campbell, USA Michael Kassiou, Australia Todd W. Vanderah, USA Hak-Kim Chan, Australia Joseph J. McArdle, USA Val J. Watts, USA Michael D. Coleman, UK Mark J. McKeage, New Zealand David J. Waxman, USA J. Descotes, France Daniel T. Monaghan, USA Dobromir Dobrev, Germany T. Narahashi, USA Plant Biotechnology Prem L. Bhalla, Australia Metin Guru, Turkey Yong Pyo Lim, Republic of Korea J. R. Botella, Australia H. M. Haggman,¨ Finland Gopi K. Podila, USA Elvira Gonzalez De Mejia, USA Liwen Jiang, Hong Kong Ralf Reski, Germany Shi-You Ding, USA P. B. Kirti, India Sudhir Sopory, India Toxicology Michael Aschner, USA Hartmut Jaeschke, USA Qaisar Mahmood, Pakistan Juergen Buenger, Germany Y. James Kang, USA R. S. Tjeerdema, USA Michael L. Cunningham, USA M. Firoze Khan, USA Kenneth Turteltaub, USA Laurence D. Fechter, USA Pascal Kintz, France Brad Upham, USA Virology Nafees Ahmad, USA Fred Kibenge, Canada Ralf Wagner, Germany Edouard Cantin, USA Fenyong Liu, USA Jianguo Wu, China Ellen Collisson, USA Eric´ Rassart, Canada Decheng Yang, Canada Kevin M. Coombs, Canada Gerald G. Schumann, Germany Jiing-Kuan Yee, USA Norbert K. Herzog, USA Y.-C. Sung, Republic of Korea Xueping Zhou, China Tom Hobman, Canada Gregory Tannock, Australia Wen-Quan Zou, USA Shahid Jameel, India Contents Mercury Toxicity,Joao˜ B. T. Rocha, Michael Aschner, JoseG.D´ orea,´ Sandra Ceccatelli, Marcelo Farina, and Luiz Carlos L. Silveira Volume 2012, Article ID 831890, 2 pages Mercury Toxicity on Sodium Pump and Organoseleniums Intervention: A Paradox, Ige Joseph Kade Volume 2012, Article ID 924549, 12 pages Role of Calcium and Mitochondria in MeHg-Mediated Cytotoxicity, Daniel Roos, Rodrigo Seeger, Robson Puntel, and Nilda Vargas Barbosa Volume 2012, Article ID 248764, 15 pages Dietary Mercury Exposure Resulted in Behavioral Differences in Mice Contaminated with Fish-Associated Methylmercury Compared to Methylmercury Chloride Added to Diet, Jean-Paul Bourdineaud, Masumi Marumoto, Akira
Recommended publications
  • ECETOC Guidance on Dose Selection
    ECETOC Guidance on Dose Selection Technical Report No. 138 EUROPEAN CENTRE OFOR EC TOXICOLOGY AND TOXICOLOGY OF CHEMICALS ECETOC Guidance on Dose Selection ECETOC Guidance on Dose Selection Technical Report No. 138 Brussels, March 2021 ISSN-2079-1526-138 (online) ECETOC TR No. 138 1 ECETOC Guidance on Dose Selection 224504 ECETOC Technical Report No. 138 © Copyright – ECETOC AISBL European Centre for Ecotoxicology and Toxicology of Chemicals Rue Belliard 40, B-1040 Brussels, Belgium. All rights reserved. No part of this publication may be reproduced, copied, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the copyright holder. Applications to reproduce, store, copy or translate should be made to the Secretary General. ECETOC welcomes such applications. Reference to the document, its title and summary may be copied or abstracted in data retrieval systems without subsequent reference. The content of this document has been prepared and reviewed by experts on behalf of ECETOC with all possible care and from the available scientific information. It is provided for information only. ECETOC cannot accept any responsibility or liability and does not provide a warranty for any use or interpretation of the material contained in the publication. ECETOC TR No. 138 2 ECETOC Guidance on Dose Selection ECETOC Guidance on Dose Selection Table of Contents 1. SUMMARY 6 2. INTRODUCTION, BACKGROUND AND PRINCIPLES 9 2.1. Background and Principles 9 2.2. Current Regulatory Framework and Guidance 10 2.2.1. Historical perspectives and the evolution of test guidelines 10 2.2.2.
    [Show full text]
  • Interaction Profile
    INTERACTION PROFILE FOR: PERSISTENT CHEMICALS FOUND IN FISH (CHLORINATED DIBENZO-p-DIOXINS, HEXACHLOROBENZENE, p,p’-DDE, METHYLMERCURY, and POLYCHLORINATED BIPHENYLS) U.S. Department of Health and Human Services Public Health Service Agency for Toxic Substances and Disease Registry May 2004 iii ACKNOWLEDGMENT The Agency for Toxic Substances and Disease Registry (ATSDR) wishes to thank the U.S. Environmental Protection Agency (EPA) for its support in the production of this Interaction Profile. v PREFACE The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) mandates that the Agency for Toxic Substances and Disease Registry (ATSDR) shall assess whether adequate information on health effects is available for the priority hazardous substances. Where such information is not available or under development, ATSDR shall, in cooperation with the National Toxicology Program, initiate a program of research to determine these health effects. The Act further directs that where feasible, ATSDR shall develop methods to determine the health effects of substances in combination with other substances with which they are commonly found. To carry out the legislative mandate, ATSDR’s Division of Toxicology (DT) has developed and coordinated a mixtures program that includes trend analysis to identify the mixtures most often found in environmental media, in vivo and in vitro toxicological testing of mixtures, quantitative modeling of joint action, and methodological development for assessment of joint toxicity. These efforts are interrelated. For example, the trend analysis suggests mixtures of concern for which assessments need to be conducted. If data are not available, further research is recommended. The data thus generated often contribute to the design, calibration or validation of the methodology.
    [Show full text]
  • Comparison of Selected in Vitro Assays for Assessing the Toxicity of Chemicals and Their Mixtures
    COMPARISON OF SELECTED IN VITRO ASSAYS FOR ASSESSING THE TOXICITY OF CHEMICALS AND THEIR MIXTURES Rola Azzi A thesis submitted for the degree of Doctor of Philosophy Chemical Safety and Applied Toxicology Laboratories School of Safety Science Faculty of Science The University of New South Wales June 2006 Certificate of Originality Certificate of Originality I hereby declare that this submission is my own work and that, to the best of my knowledge it contains no materials previously published or written by another person, nor material which to a substantial extent has been accepted for the award of any degree at UNSW or any other education institution, except where due acknowledgment is made in the thesis. Any contributions made to the research by others, which whom I have worked, is explicitly acknowledged in the thesis. I also declare that the intellectual content of this thesis is the product of my own work, except to the extent that assistance from others in the project’s design and conception or in style, presentation and linguistic expression is acknowledged. Rola Azzi June 2006 i Acknowledgments Acknowledgments I would like to express my sincerest gratitude to my supervisor Dr Amanda Hayes for her assistance, constant encouragement and expertise. Without her support and guidance this project would not have been possible. I am also grateful to Associate Professor Chris Winder, for his constant support, advice, and scientific expertise throughout my work on this project. I would also like to express my sincerest gratitude and appreciation to my uncle, Associate Professor Rachad Saliba, who was a constant support during the writing of this thesis, and was devoted to helping me grasp the science of statistics, and its ability to transform numbers into a story.
    [Show full text]
  • Toxicological Profile for Zinc
    TOXICOLOGICAL PROFILE FOR ZINC U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Agency for Toxic Substances and Disease Registry August 2005 ZINC ii DISCLAIMER The use of company or product name(s) is for identification only and does not imply endorsement by the Agency for Toxic Substances and Disease Registry. ZINC iii UPDATE STATEMENT A Toxicological Profile for Zinc, Draft for Public Comment was released in September 2003. This edition supersedes any previously released draft or final profile. Toxicological profiles are revised and republished as necessary. For information regarding the update status of previously released profiles, contact ATSDR at: Agency for Toxic Substances and Disease Registry Division of Toxicology/Toxicology Information Branch 1600 Clifton Road NE Mailstop F-32 Atlanta, Georgia 30333 ZINC vi *Legislative Background The toxicological profiles are developed in response to the Superfund Amendments and Reauthorization Act (SARA) of 1986 (Public law 99-499) which amended the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA or Superfund). This public law directed ATSDR to prepare toxicological profiles for hazardous substances most commonly found at facilities on the CERCLA National Priorities List and that pose the most significant potential threat to human health, as determined by ATSDR and the EPA. The availability of the revised priority list of 275 hazardous substances was announced in the Federal Register on November 17, 1997 (62 FR 61332). For prior versions of the list of substances, see Federal Register notices dated April 29, 1996 (61 FR 18744); April 17, 1987 (52 FR 12866); October 20, 1988 (53 FR 41280); October 26, 1989 (54 FR 43619); October 17, 1990 (55 FR 42067); October 17, 1991 (56 FR 52166); October 28, 1992 (57 FR 48801); and February 28, 1994 (59 FR 9486).
    [Show full text]
  • Toxicological Profile for Copper
    TOXICOLOGICAL PROFILE FOR COPPER U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Agency for Toxic Substances and Disease Registry September 2004 COPPER ii DISCLAIMER The use of company or product name(s) is for identification only and does not imply endorsement by the Agency for Toxic Substances and Disease Registry. COPPER iii UPDATE STATEMENT A Toxicological Profile for Copper, Draft for Public Comment was released in September 2002. This edition supersedes any previously released draft or final profile. Toxicological profiles are revised and republished as necessary. For information regarding the update status of previously released profiles, contact ATSDR at: Agency for Toxic Substances and Disease Registry Division of Toxicology/Toxicology Information Branch 1600 Clifton Road NE, Mailstop F-32 Atlanta, Georgia 30333 COPPER vii QUICK REFERENCE FOR HEALTH CARE PROVIDERS Toxicological Profiles are a unique compilation of toxicological information on a given hazardous substance. Each profile reflects a comprehensive and extensive evaluation, summary, and interpretation of available toxicologic and epidemiologic information on a substance. Health care providers treating patients potentially exposed to hazardous substances will find the following information helpful for fast answers to often-asked questions. Primary Chapters/Sections of Interest Chapter 1: Public Health Statement: The Public Health Statement can be a useful tool for educating patients about possible exposure to a hazardous substance. It explains a substance’s relevant toxicologic properties in a nontechnical, question-and-answer format, and it includes a review of the general health effects observed following exposure. Chapter 2: Relevance to Public Health: The Relevance to Public Health Section evaluates, interprets, and assesses the significance of toxicity data to human health.
    [Show full text]
  • (GIVIMP) for the Development and Implementation of in Vitro Methods for 829 Regulatory Use in Human Safety Assessment
    1 2 Draft GUIDANCE DOCUMENT ON GOOD IN VITRO METHOD PRACTICES (GIVIMP) 3 FOR THE DEVELOPMENT AND IMPLEMENTATION OF IN VITRO METHODS FOR 4 REGULATORY USE IN HUMAN SAFETY ASSESSMENT 5 6 FOREWORD 7 8 A guidance document on Good In Vitro Method Practices (GIVIMP) for the development and 9 implementation of in vitro methods for regulatory use in human safety assessment was 10 identified as a high priority requirement. The aim is to reduce the uncertainties in cell and 11 tissue-based in vitro method derived predictions by applying all necessary good scientific, 12 technical and quality practices from in vitro method development to in vitro method 13 implementation for regulatory use. 14 The draft guidance is coordinated by the European validation body EURL ECVAM and has 15 been accepted on the work plan of the OECD test guideline programme since April 2015 as a 16 joint activity between the Working Group on Good Laboratory Practice (GLP) and the 17 Working Group of the National Coordinators of the Test Guidelines Programme (WNT). 18 The draft document prepared by the principal co-authors has been sent in September 2016 to 19 all 37 members of the European Union Network of Laboratories for the Validation of 20 Alternative Methods (EU-NETVAL1) and has been subsequently discussed at the EU- 21 NETVAL meeting on the 10th of October 2016. 22 By November/December 2016 the comments of the OECD Working Group on GLP and 23 nominated experts of the OECD WNT will be forwarded to EURL ECVAM who will 24 incorporate these and prepare an updated version.
    [Show full text]
  • “Six-Pack” Testing Strategy: Influx of Modern in Vitro Techniques Gertrude-Emilia Costin, Ph.D., M.B.A
    Modernizing the “six-pack” testing strategy: influx of modern in vitro techniques Gertrude-Emilia Costin, Ph.D., M.B.A. Institute for In Vitro Sciences, Inc. (IIVS) NorCal SOT Fall Symposium 2017 The 3Rs 28 September 2017, San Francisco, CA, USA Perspectives, challenges, common goals and working together Safety/ Testing Labs Labeling/ Industry/ Regulatory Manufacturer Agency Consumer/ End-user Safety Presentation Outline Current regulatory climate – global acceptance of in vitro methods The reductionist concept of in vitro methods Drivers of in vitro methods advancement Beyond the “six-pack” battery of acute toxicity tests Acute oral toxicity Acute dermal toxicity (oral vs dermal route comparison) Acute inhalation toxicity Ocular irritation (the EPA OPP testing strategy) Skin irritation/corrosion Skin sensitization Modernizing the “six-pack” testing strategy: influx of modern in vitro techniques Current regulatory climate – global acceptance of in vitro methods The reductionist concept of in vitro models 1940s 1990s Whole animal Organ - Eyeball Tissue - Cornea Cell culture (Rabbit) (Enucleated chicken or (Resected bovine (Statens Seruminstitut rabbit eye) cornea) Rabbit cornea cells) “Less is more” Retinal Pigment Epithelium Semi-permeable Membrane Vascular network Nutrient channels Fibrinogen- endothelial cell administration channel Body-on-a-chip Organ-on-a-chip Tissue construct Cell culture (Human organotypic (Human retina) (Human EpiCorneal™ (Normal human microtissues) model) corneal epithelial cells) 2010s 2000s G.-E. Costin and H. A. Raabe. In vitro toxicology models. In: The Role of the Study Director in Non-clinical Studies. Pharmaceuticals, Chemicals, Medical Devices, and Pesticides. (Eds. William Brock, Barbara Mounho and Lijie Fu), John Wiley and Sons (2014). G.-E. Costin.
    [Show full text]
  • In Vitro Toxicology Cytotoxicity and Mechanism
    In vitro Toxicology Cytotoxicity and Mechanism Introduction ImQuest BioSciences offers a panel of in vitro assays to evaluate the cyto- toxicity and mechanism of cytotoxicity of potential pharmaceutical prod- ucts. In vitro cytotoxicity assays are used to predict the toxicity of com- pounds as well as to identify potential safety and development problems prior to in vivo safety and toxicology evaluations. Together with infor- mation on the drug candidate’s efficacy and pharmaceutical properties, the results may be used to select lead compounds that will be given pref- erence for progression to animal studies and IND-directed development. In addition, in vitro toxicity assays provide preliminary information about the mechanisms of toxicity likely to be observed during in vivo studies. To assess the effects of test compounds on cell viability, cell proliferation and macromolecule synthesis, ImQuest’s cytotoxicity evaluations are per- formed with a number of human immune system cell types and cell types representative of the major functional organ systems. Examples of these cell types include: peripheral blood mononuclear cells (PBMCs), mono- cyte-macrophages, dendritic cells, bone marrow progenitor cells, primary hepatocytes, induced pluripotent stem cell (iPS) cardiomyocytes, iPS neu- Technological advances rons and renal proximal tubule cells (RPTEC). have increased the effec- tiveness of in vitro toxi- Mechanism of cytotoxicity assays are used to evaluate the effect of test cology analysis: compounds on the cell cycle, mitochondrial respiration and function, Pluripotent stem cells apoptosis, membrane integrity and oxidative stress. These assays are that can be directed to used to analyze the predominant areas where a test compound may exert differentiate into various an adverse effect.
    [Show full text]
  • Alternatives to and Reduction of Animal Use in Biomedical Research, Education and Testing
    WellBeing International WBI Studies Repository 1990 Alternatives to and Reduction of Animal Use in Biomedical Research, Education and Testing John M. Frazier Johns Hopkins University Alan M. Goldberg Johns Hopkins University Follow this and additional works at: https://www.wellbeingintlstudiesrepository.org/acwp_arte Part of the Bioethics and Medical Ethics Commons, Laboratory and Basic Science Research Commons, and the Research Methods in Life Sciences Commons Recommended Citation Frazier, J. M., & Goldberg, A. M. (1990). Alternatives to and reduction of animal use in biomedical research, education and testing. Alternatives to laboratory animals: ATLA. This material is brought to you for free and open access by WellBeing International. It has been accepted for inclusion by an authorized administrator of the WBI Studies Repository. For more information, please contact [email protected]. Alternatives to and Reduction of Animal Use in Biomedical Research, Education and Testing John M. Frazier and Alan M. Goldberg Johns Hopkins University KEYWORDS animal experimentation, animal testing, alternatives ABSTRACT Biomedical endeavours can be divided into three major categories: research, education, and testing. Within the context of each of these categories, activities involving whole animals have made major contributions and will continue to do so in the future. However, with technological developments in the areas of biotechnology and computers, new methods are already reducing the use of whole animals in certain areas. This article discusses the general tissues of alternatives and then focuses on the development of new approaches to toxicity testing. Introduction In recent years, societal concerns over the use of animals in various biomedical activities have significantly increased. The ethical issues involved are not new; however, increased awareness of these issues in the scientific community has led to an increased emphasis on the development of new approaches to conducting these traditional activities (1).
    [Show full text]
  • Mechanisms of Cell Toxicity and in Vitro Toxicology
    Mechanisms of cell toxicity and in vitro toxicology Nik Hodges School of Biosciences [email protected] Cell Toxicity The dose “makes” the poison "dosis sola facit venenum" - dosage alone makes the poison. Dose-response curves Dead Depressed breathing Unconscious Deep Sleep Asleep R “ e s Giddy p o n Happy s e ” No effect Dose (at target tissue) How do cells die ? Necrosis Molecular pathways involved in apoptosis e.g. osmotic * Doesn’t require energy * Unregulated * Damaging to surrounding cells Likely effect of detergents Adaptation Apoptosis Necrosis Concentration Measuring cell death MTT assay Mitochondrial function Cyt c Caspase 3/7 N Adenylate kinase (AK) assay Membrane integrity How do chemicals cause toxicity ? 1) 3D Shape: enzyme inhibition receptor mediated effects - activation of transcription factors resulting in inappropriate changes in gene expression other specific interactions 2) Reactivity: covalent binding DNA - mutations - cancer Protein - altered protein function – immune responses reaction with other biomolecules -depletion of protective factors glutathione depletion lipid peroxidation *Interfere with/compromise normal cellular functioning* Why is it important to understand the mechanism of toxicity ? Understanding of mechanism facilitates: • Extrapolation of animal data and in vitro data to the humans • Biological monitoring and screening • Understanding and predicting toxicity of new substances • Risk assessment • Make chemicals safer Chemical Metabolism Detoxification Toxic Metabolite Cellular targets Adaptive response
    [Show full text]
  • In Vitro Liver Toxicity Testing of Chemicals: a Pragmatic Approach
    International Journal of Molecular Sciences Review In Vitro Liver Toxicity Testing of Chemicals: A Pragmatic Approach Andrés Tabernilla † , Bruna dos Santos Rodrigues †, Alanah Pieters , Anne Caufriez , Kaat Leroy, Raf Van Campenhout , Axelle Cooreman, Ana Rita Gomes, Emma Arnesdotter , Eva Gijbels and Mathieu Vinken * Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium; [email protected] (A.T.); [email protected] (B.d.S.R.); [email protected] (A.P.); [email protected] (A.C.); [email protected] (K.L.); [email protected] (R.V.C.); [email protected] (A.C.); [email protected] (A.R.G.); [email protected] (E.A.); [email protected] (E.G.) * Correspondence: [email protected]; Tel.: +32-2-477-45-87 † Both authors contributed equally. Abstract: The liver is among the most frequently targeted organs by noxious chemicals of diverse nature. Liver toxicity testing using laboratory animals not only raises serious ethical questions, but is also rather poorly predictive of human safety towards chemicals. Increasing attention is, therefore, being paid to the development of non-animal and human-based testing schemes, which rely to a great extent on in vitro methodology. The present paper proposes a rationalized tiered in vitro testing strategy to detect liver toxicity triggered by chemicals, in which the first tier is focused on assessing general cytotoxicity, while the second tier is aimed at identifying liver-specific toxicity as such. A state-of-the-art overview is provided of the most commonly used in vitro assays that can be used in Citation: Tabernilla, A.; dos Santos both tiers.
    [Show full text]
  • Toxicogenomics
    Journal of Bioinformatics and Sequence Analysis Vol. 2(4), pp. 42-46, August 2010 Available online at http://www.academicjournals.org/jbsa DOI: 10.5897/JBSA09.033 ISSN 2141-2464 ©2010 Academic Journals Review Toxicogenomics S. Amala Department of Biotechnology and Bioinformatics, Dhanalakshmi Srinivasan, College of Arts and Science for Women, Perambalur-621212, Tamil Nadu, India. E-mail:[email protected]. Accepted 21 June, 2010 The field of toxicology is defined as the study of stressors and their adverse effects. One discipline should deals with hazard identification, mechanistic toxicology, and risk assessment. Thus emerge a new field called toxicogenomics. Toxicogenomics is a rapidly developing discipline that promises to aid scientists in understanding the molecular and cellular effects of chemicals in biological systems. This is a comparatively new field of biological inquiry now providing insights into the toxic effects of chemicals on biological systems and helping investigators to predict risks associated with exposure to these agents. This field encompasses global assessment of biological effects using technologies such as DNA micro arrays or high throughput NMR and protein expression analysis. Key words: Genomics, toxicogenomics, toxicology. INTRODUCTION The rapid evolution of genome-based technologies has WHAT IS TOXICOGENOMICS? greatly accelerated the application of gene expression profiling in toxicology studies. These technological Toxicogenomics is a field of science that deals with the advances have led to the development of the field of collection, interpretation, and storage of information about toxicogenomics, which proposes to apply mRNA gene and protein activity within particular cell or tissue of expression technologies to study effects of hazards in an organism in response to toxic substances.
    [Show full text]