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Information sources in toxicology While there are many journals, books, and online databases that specifically publish toxicology information and results of toxicological studies, toxicology by nature is a transdisciplinary field. Toxicologists draw information from many fields of evolving science including medicine, pharmacology, physiology, biochemistry, biology, genetics and epigenetics, chemistry, and physics. Toxicologists thus have access to a rich body of scientific literature. For this introductory book, it was not the intent of the authors to compile a comprehensive list of toxicology recourses. Rather, it was our intent to provide a selected list of useful reference texts and review articles. We also provide a list and brief description of the most common computer database systems used by toxicologists. Together, these resources should provide a good place for readers to begin more in-depth reading and research.
Primary scientific literature As in any field of science, the most reliable source of information is the published, peer-reviewed literature. These journals report the results of scientific studies performed around the world by academic, government, industry, and other nonprofit research laboratories. Before the results are accepted for publication, they must undergo a rigorous peer review process. This process is managed by the journals who appoint an editor in chief, editors, and associate editors, who are usually the leading experts in their fields. Manuscripts are submitted by authors to a journal of their choosing. The editorial team then selects appropriate experts to review the manuscript. The review process includes a detailed evaluation of the scientific methods, results, statistical validity, data interpretation, and conclusions reached by the authors. In most cases, the reviewers suggest changes and additional experiments before the manuscript can be considered for publication. Manuscripts are also ranked on appropriateness for the journal, quality of the science relative to published papers, and impact on the field. Once reviewers recommend publication, the editorial team will make a final decision on whether or not to publish the manuscript. This scientific process has been sustained for hundreds of years and is self-correcting. Data that were in error, or rarely fabricated by the authors, are invariably revealed, as all science builds on previous findings. Loomis’s Essentials of Toxicology. https://doi.org/10.1016/B978-0-12-815921-7.00015-6 © 2020 Elsevier Inc. All rights reserved.
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The primary literature now comprises almost 30,000 scientific journals that are generally published on a weekly or monthly basis. One estimate puts the number of scientific papers published annually at 1.8 million. Fortunately, publishers have migrated to online publication over the last two decades. Access to the scientific literature databases allows almost instantaneous searching for all papers on a given topic from any computer. Many journals are no longer published as hard copies that sit on library shelves collecting dust. There has also been a move toward open access journals. While traditional publishers only provide access to individual researchers or libraries that pay a subscription fee, open access journals allow access to all investigators free of charge. Costs are offset by charging the authors a substantial publication fee. Given the value of open access to rapidly and widely distributing scientific findings, most traditional publishers now used a mixed model that gives the option of publishing papers as open access. Unfortunately, the popularity of open access and the lucrative nature of publishing for a fee have spawned thousands of new journals. An increasing number of these do not adhere to the ethical and expected standards of scientific publication, publishing essentially all papers submitted. This does not say that all open access journals are unreliable. Readers can usually avoid these predatory journals by referencing papers published in journals with editorial boards composed of renowned scientific leaders, those whose published impact factors that are robust, and those associated with profession scientific societies.
Secondary sources of information In addition to the primary literature, there exists a vast body of information in the form of textbooks, review articles, special reports, monographs, opinion pieces such as letters to the editors, handbooks, and a compendium of electronic databases. These secondary resources do not create scientific information; rather, they are mechanisms for locating, referencing, organizing, systematizing, condensing, abstracting, or reviewing the primary journal literature. Each is a product of a third party and therefore subject to errors of omission and commission. They are a starting point for retrieving scientific facts from peerreviewed sources. It is therefore important for students and investigators to verify crucial facts by reading the original sources in the primary journal literature. These secondary sources have the advantage that the authors have already considered a large fragment of the primary literature, including existing controversies. Considering whenever a search of the primary literature is conducted, the investigator will become aware of apparent conflicts in opinions or conclusions. This condition can be confusing to a new investigator. Often, the original sources of data as reported in the primary literature do not conflict; rather, differences are due to interpretation and extrapolation of data without proper precautions. In other instances, discrepancies can often be explained by variations in study design or experimental parameters. This is usually brought to light and
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discussed in well-written secondary publications. Thus, an additional advantage of beginning a literature review by reading the secondary literature is that they usually address discrepancies, controversies, and differences of opinion. These insights will allow readers to select the most appropriate studies and data for further investigation.
Compendia of toxicology resources The cornucopia of toxicology resources available in print and online has become almost overwhelming to those new to the field and seasoned veterans. When information is sought, it is often difficult to decide where to begin the search. In the 21st century, this usually means doing an internet-based search using one of the many powerful search engines available to everyone. However, internet search can return thousands of results, especially if the search terms are not specific, or the investigator is not sure of the right question. Fortunately, Philip Wexler took on the herculean task of putting together a compendium of information available to toxicologists in 1982. Since then, he has assumed the daunting task of editing three updated editions. The most recent one is as follows: Information Resources in Toxicology, 4th Edition Editor in chief: Philip Wexler Editors: P.J. Hakkinen, Asish Mohapatra, and Steven G. Gilbert eBook ISBN: 9780080920030 Hardcover ISBN: 9780123735935 Imprint: Academic Press Published date: July 16, 2009 Page count: 1552 This book is a sourcebook for readers who need to know where to find toxicology information. This newest edition includes extensive itemization, review, and commentary on the information infrastructure of the field. This version provides a wide-ranging, international, annotated bibliography, and compendium of major resources in toxicology and the related fields of environmental and occupational health, chemical safety, and risk assessment. The updated edition analyzes technological changes and is replete with online tools and links (URLs) to relevant web sites. The book uses a highly structured format that facilities access to information. Among the topics covered are disaster preparedness and management; omics; risk assessment; nanotechnology; the precautionary principle; and biological, chemical, and radioactive terrorism and warfare. This book is available in an inexpensive online (eBook) version. In addition, the National Institutes of Health has created the National Library of Medicine, which compiles a comprehensive list of all papers published by its grant awardees free of charge to researchers, in many cases before the journals release the papers.
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Books General toxicology Hayes’s Principles and Methods of Toxicology, 6th Edition Editors: A. Wallace Hayes and Claire L. Kruger ISBN: 978-1,842,145,364 Publisher: Taylor and Francis Published date: 09/05/2014 Page count: 2184 Casarett and Doull’s Toxicology. The Basic Science of Poisons, 9th Edition Editor: Curtis C, Klaassen ISBN: 978-1,259,863,745 Publisher: McGraw Hill Medical Published Date: November 19, 2018 Page count: 1600 Goodman and Gilman’s Pharmacological Basis of Therapeutics, 13th Edition Editors: Lawrence L. Brunton, Bjorn Knollman, and Randa Hilal-Dandan ISBN: 978-1,259,584,749 Publisher: McGraw Hill Professional Published date: October 26, 2017 Page count: 1440
Clinical toxicology Goldfrank’s Toxicologic Emergencies Editors: Lewis S. Nelson, Mary Ann Howland, Neal A. Lewin, Silas W. Smith, Lewis R. Goldfrank, and Robert S. Hoffman eBook ISBN: 978-1,259,859,618 Hardcover ISBN: 978-1,259,859,618 Publisher: McGraw Hill Education Published date: 2019 Page count: 1552 Haddad and J. F. Winchester Management of Drug Overdose, 4th Edition Editors: Michael W. Shannon, Stephen W. Borron, and Michael J. Burns ISBN: 978-0721606934 Publisher: Saunders Published date: 2007 Page count: 1584
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Industrial toxicology 2019 Threshold Limit Values and Biological Exposure Indices Editor: American Conference of Governmental Industrial Hygienists, Inc. ISBN: 978-1,607,261,056 Publisher: Signature Publications Published date: 2019 Page count: 304 Also see: https://www.chemsafetypro.com/Topics/USA/ACGIH_TLVs_ Threshold_Limit_Values.html
Risk assessment Toxicological Risk Assessment for Beginners Editors: Jose A. Torres and Sol Bobst ISBN: 978-3,319,127,507 Publisher: Springer Published date: 2015 Page count: 250 Environmental Risk Assessment: A Toxicological Approach Editor: Ted Simon ISBN: 978-1,138,033,832 Publisher: Routledge Published date: 2016 Page count: 414
Toxicogenomics Handbook of Toxicogenomics: Strategies and Applications Editor: J€ urgen Borlak ISBN: 978-3,527,604,517 Publisher: John Wiley & Sons Published date: March 6, 2006 Page count: 705 Toxicogenomics: Principles and Applications Editors: Hisham K. Hamadeh and Cynthia A. Afshari ISBN: 978-0471434177 Publisher: Wiley Published date: September 2004 Page count: 361
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Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment Authors: Committee on Applications of Toxicogenomic Technologies to Predictive Toxicology Editors: National Research Council, Division on Earth and Life Studies, Board on Life Sciences, Board on Environmental Studies and Toxicology ISBN: 978-0309112987 Publisher: National Academies Press Published date: November 19, 2007 Page count: 300 Internet Access to the National Library of Medicine’s Toxicology and Environmental Health Databases Editors: Catharyn T. Liverman, Carolyn E. Fulco, and Howard M. Kipen ISBN: 0-309-06299-3 Publisher: National Academies Press Published date: 1998 Page count: 35
Alternative methods in toxicity testing Toxicity Testing in the 21st Century. A Vision and a Strategy Authors: Committee on Toxicity Testing and Assessment of Environmental Agents Editors: Board on Environmental Studies and Toxicology Institute for Laboratory Animal Research Division on Earth and Life Studies National Research Council of the National Academies ISBN: 978-0309109925 Publisher: National Academies Press Published date: June 12, 2007 Page count: 216
Database systems POISINDEX https://truvenhealth.com/Portals/0/Assets/Brochures/International/INTL_ 12339_0614_Poisindex_A4_WEB1.pdf As part of the Micromedex Toxicology Management Solution from Truven Health Analytics, the Micromedex POISINDEX System is a reliable, evidencebased resource for identification, management, and treatment of toxic exposures. POISINDEX provides instant access to ingredient and toxic substance information on 350,000 + commercial products, chemicals, drugs, toxic plants, and animals. ToxIndex is the only system that links to other information systems such as the following: Hazardtext for hazardous compounds for incidents such as spills, leaks, fires, or explosives involving hazardous
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materials and Meditext for acute exposures to industrial chemicals. This unique capability makes POISINDEX the preferred reference of emergency first responders.
POISON CONTROL CENTERS https://aapcc.org Poison Help: 1-800-222-1222
NATIONAL LIBRARY OF MEDICINE https://www.nlm.nih.gov/about/index.html The National Library of Medicine (NLM) was founded in 1836 by National Institutes of Health in Bethesda, Maryland. NLM is the world’s largest biomedical library with an extensive collection in print. The NLM also produces electronic information resources on a wide range of topics that are searched billions of times each year by millions of people from around the world. In addition, the library coordinates a 6500-member National Network of Libraries of Medicine that promotes and provides access to health information in communities across the United States. The NLM compiles a complete list of all papers published by its grant awardees in an open access, in many cases before the journals release the papers to researchers free of charge.
TOXLINE https://toxnet.nlm.nih.gov/newtoxnet/toxline.htm Toxicology Information Online (TOXLINE) was established by the Toxicology Information Program of the NLM. It consists of a vast collection of bibliographic files containing millions of citations on virtually all aspects of toxicology. TOXLINE is a bibliographic database with citations from a wide variety of specialized journals and other sources. The database includes publications from the fields of biochemical, pharmacological, physiological, and toxicological effects of drugs and chemicals. Most of citations include abstracts and/or indexing terms and Chemical Abstract Service (CAS) Registry Numbers. TOXLINE includes references beginning in the 1840s to the present and is updated weekly.
TOXNET https://toxnet.nlm.nih.gov Toxicology Data Network (TOXNET) is produced by the Toxicology Information Program of the NLM. The database provides access to Hazardous Substances Data Bank (HSDB) Information Sources in Toxicology, Registry of Toxic Effects of Chemical Substances (RTECS), Chemical Carcinogenesis Research Information System (CCRIS), Environmental Teratology Information
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Center Backfile (ETICBACK), Environmental Mutagenesis Information Center Backfile (EMICBACK), Directory of Biotechnology Information Resources (DBIR), Toxic Chemical Release Inventory (TRI), Developmental and Reproductive Toxicology file (DART), Genetic Toxicology (GENETOX) database, and the EPA Integrated Risk Information System (IRIS). TOXNET also permits the user to create and maintain chemical records online and allows interactive review and editing of data records.
Computational Resources for Quantitative Structure-Activity Relationships (QSAR) http://crdd.osdd.net/qsar.php http://vega.marionegri.it/wordpress/wp-content/uploads/2011/09/chap8.pdf Quantitative structural-activity relationship (QSAR) quantitatively correlates the structure of molecule (descriptors) with their physicochemical properties, biological activities, and toxicity. The method uses statistical analyses (e.g., multiple linear regression, partial least square, support vector machines, artificial neural network, decision trees, and Bayesian classifier) to generate mathematical models that relate a set of chemical descriptors to experimentally measured parameters. QSAR models are then used to predict biological activities and undesired effects of untested or novel compounds and to provide insight into relevant and consistent chemical properties or structural features that define biological activity. Once a series of predicted models are collected, QSAR can also be used to mine database to identify candidate compounds with specific biological activities, particularly, for those having drug-like properties and suitable pharmacokinetic properties.
The OECD QSAR Toolbox http://www.oecd.org/chemicalsafety/risk-assessment/oecd-qsar-toolbox.htm To increase the regulatory acceptance of (Q)SAR methods, the Organization for Economic Cooperation and Development (OECD) has developed a QSAR Toolbox to make (Q)SAR technology readily accessible, transparent, and less expensive. The toolbox provides a robust compilation of software, databases, websites for QSARs and for the European Union’s Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH).
PUBMED https://www.nlm.nih.gov/bsd/pubmed.html PUBMED is a free resource developed and maintained by the National Center for Biotechnology Information (NCBI) at the NLM. PubMed provides free access to Medline; NLM’s database of citations; and abstracts in the fields of medicine, nursing, dentistry, veterinary medicine, health care systems, and preclinical sciences. The database also includes citations to some additional
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life science journals that submit full-text articles to PUBMED Central and receive a qualitative review by NLM. The resource has citations for the majority of books and book chapters available on the NCBI Bookshelf. Links to full-text articles are found in PUBMED Central or at publisher web sites. The recourse also provides advanced search, clinical queries search filters, and special queries pages. PUBMED includes discovery tools to find related papers of interest and provides links to NCBI molecular biology resources. The database is updated daily.
Medical Information online (MEDLINE) https://www.nlm.nih.gov/bsd/medline.html MEDLINE is the NLM’s most extensive bibliographic database. The database contains more than 25 million references to journal articles primarily in the life sciences. MEDLINE records are indexed with NLM Medical Subject Headings (MeSH). MEDLINE is the online version to MEDical Literature Analysis and Retrieval System (MEDLARS) that was initiated in 1964. MEDLINE is the primary component of PUBMED, part of the Entrez series of databases provided by the NCBI. The database includes publications from 1966 to present, with limited coverage prior to that period. Citations are compiled from more than 5200 worldwide journals in about 40 languages. Citations are added to PubMed 7 days a week. More than 904,636 citations were added to MEDLINE in 2018. On their web page, MEDLINE indicates that the subject scope of their database is “biomedicine and health, broadly defined to encompass those areas of the life sciences; behavioral sciences; chemical sciences; and bioengineering needed by health professionals and others engaged in basic research and clinical care, public health, health policy development, or related educational activities. MEDLINE also covers life sciences vital to biomedical practitioners, researchers, and educators, including aspects of biology, environmental science, marine biology, plant and animal science, and biophysics and chemistry.”
BIOSIS https://clarivate.libguides.com/webofscienceplatform/bci https://clarivate.libguides.com/webofscienceplatform/introduction BIOSIS Citation Index is part of the Web of Science, a platform consisting of literature search databases designed to support scientific and scholarly research. BIOSIS combines indexed life science coverage found in BIOSIS Previews (biological abstracts, reports, reviews, and meetings) with searching tools for references in 5300 journals and over 165,000 items from more than 1500 meetings (1926–present). Subject coverage includes traditional areas of biology like botany, zoology, and microbiology. Interdisciplinary areas of science including agriculture, biochemistry, bioengineering, biomedical, biophysics, biotechnology, ecology, medicine, and pharmacology are also covered.
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International Pharmaceutical Abstracts https://health.ebsco.com/products/international-pharmaceutical-abstracts Produced by Clarivate Analytics, this database provides extensive indexing and abstracts for pharmaceutical and medical journals published worldwide. The database includes more than 500,000 abstracted and indexed records from more than 800 global journals dating back to 1970. Subjects covered include biopharmaceuticals and pharmacokinetics; legal, political, and ethical issues; new drug delivery systems; and pharmacist liability.
Government and regulatory agencies Organization for Economic Cooperation and Development (OECD) https://www.oecd.org/about/ The mission of the OECD is to promote policies that can improve the economic and social well-being of people around the world. The OECD was established in 1960s when 18 European countries plus the United States and Canada joined forces to create an organization. Today, the OECD is a group of 36 member countries around the globe that discuss and develop economic and social policies. The OECD provides a forum for governments to cooperate, share experiences, and seek solutions to common problems. OECD sets international standards on a wide range of matters from agriculture and taxes to the safety of chemicals.
USA Food and Drug Administration (FDA) https://www.fda.gov https://open.fda.gov/ The FDA is a federal agency of the US Department of Health and Human Services. The FDA is responsible for protecting public health through the regulations of food safety, dietary supplements, prescription and over-the-counter (OTC) medications, vaccines, biologics, blood transfusions, medical devices, electromagnetic radiation-emitting devices, cosmetics, tobacco products, animal food, and veterinary products. FDA scientific committees provide evidence-based recommendations on medicines for human and veterinary use and other areas of regulatory interest to the agency. The agency provides marketing authorization and monitors veracity of advertising and postmarketing pharmacovigilance. The agency also coordinates inspections in connection with the assessment of marketing authorization applications or matters referred to its committees. The FDA has collected a large amount of data through the decades. In 2013, OpenFDA was created to enable the public to have easy access to such data. The ultimate goal of data sharing is to educate people and save lives.
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European Medical Agency (EMA) https://www.ema.europa.eu The mission of the EMA is to foster scientific excellence in the evaluation and supervision of medicines for the benefit of public and animal health in the European Union (EU). EMA is the European counterpart of the US FDA. EMA enables timely development and patient access to new medicines for the benefit of patients. The agency also supports research and innovation in the pharmaceutical sector and promotes innovation and development of new medicines. EMA’s scientific committees provide evidence-based recommendations on medicines for human and veterinary use. The agency’s evaluation of marketing authorization is the basis for the authorization of medicines in the European Union. EMA also coordinates inspections in connection with the assessment of marketing authorization applications. EMA continuously monitors and supervises the safety of medicines that have been authorized in the EU to ensure that their benefits outweigh their risks. The agency also monitors industry compliance with their pharmacovigilance obligations.
Registration, Evaluation, Authorization and Restriction of Chemicals (REACH), European Union http://ec.europa.eu/environment/chemicals/reach/background/index_en.htm The goal of REACH (EC 1907/2006) is to improve protection of human health and the environment through early identification of the intrinsic hazard of chemicals. REACH meets these goals through registration, evaluation, authorization, and restriction of chemicals. REACH also seeks to enhance innovation and competitiveness in the EU chemical industry via the “No data, no market” rule. REACH places responsibility for managing risks from chemical exposures in industries and provides safety information on the substances. Manufacturers and importers must gather information on the properties of chemical substances to ensure safe handling. They are also required to register the information in a central database in the European Chemicals Agency (ECHA) in Helsinki, Finland. ECHA manages the necessary database systems, coordinates evaluation of suspicious chemicals, and provides a public database in which consumers and professionals can find hazard information. Reach also calls for the progressive substitution of the most dangerous chemicals (referred to as “substances of very high concern”) with suitable alternatives.
Agency for Toxic Substances and Disease Registry (ATSDR) https://www.atsdr.cdc.gov The registry (ATSDR) is a federal public health agency within the US Department of Health and Human Services. The mission of the agency is to protect communities from harmful health effects related to exposure to natural and
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man-made hazardous substances. ATSDR responds to environmental health emergencies, investigates emerging environmental health threats, conducts research on the health impacts of hazardous waste sites, and provides actionable guidance to state and local health partners.
US Environmental Protection Agency (EPA) https://www.epa.gov The mission of the EPA is to protect human health and the environment. The EPA is responsible for environmental stewardship and ensures that Americans have clean air, land, and water. The agency’s leading efforts to reduce environmental risks are based on the best available scientific information. The EPA enforces Federal laws to protect human health and the environment communities. The EPA oversees the cleanup of contaminated lands and toxic sites. The EPA works with businesses, nonprofit organizations, and state and local governments through partnerships on conserving water and energy, minimizing greenhouse gases, reusing solid waste, and getting a handle on pesticide risks. The EPA shares information and publicly recognizes its partners.
Integrated Risk Information System (IRIS) https://www.epa.gov/iris EPA’s IRIS program supports EPA’s mission by identifying and characterizing the health hazards of chemicals found in the environment. Each IRIS assessment can cover a chemical, a group of related chemicals, or a complex mixture. IRIS assessments determine the following toxicity values for health effects resulting from chronic exposure to chemicals: (1) reference Dose (RfD), an estimated daily oral exposure to the human population that is likely to be without an appreciable risk of deleterious effects during a lifetime; (2) reference Concentration (RfC), an estimated daily exposure by inhalation that is likely to be without an appreciable risk of deleterious effects during a lifetime; (3) cancer descriptors; (4) oral slope factor (OSF), an estimate of the increased cancer risk from oral exposure to a dose of 1 mg/kg/day for a lifetime; and (5) inhalation unit risk (IUR), an estimate of the increased cancer risk from inhalation exposure to a concentration of 1 μg/m3 for a lifetime.
Occupational Safety and Health Administration (OSHA) https://www.osha.gov/about.html OSHA is part of the US Department of Labor. The US Congress created OSHA in 1970 to ensure safer and healthy working environments for working men and women. OSHA sets and enforces standards and provides training, outreach, education, and assistance. The OSH Act covers most private sector employers and their workers, some public sector employers and workers in
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the 50 states and certain territories, and jurisdictions under federal authority including the District of Columbia, Puerto Rico, the Virgin Islands, American Samoa, Guam, Northern Mariana Islands, Wake Island, Johnston Island, and the Outer Continental Shelf Lands as defined in the Outer Continental Shelf Lands Act.
The National Institute for Occupational Safety and Health (NIOSH) https://www.cdc.gov/niosh/about/default.html https://www.aiha.org/Pages/default.aspx Under the jurisdiction of the Centers for Disease Control and Prevention, NIOSH develops and translates new knowledge in the field of occupational safety and health. NIOSH seeks to reduce worker illness and injury and to advance worker well-being by tracking work-related hazards, exposures, illnesses, and injuries for prevention. NIOSH promotes safe and healthy workers through research interventions, recommendations, capacity building and global collaborations.
Toxic Substances Control Act (TSCA) https://www.epa.gov/chemicals-under-tsca Chemicals regulated by TSCA include many products that we use in our everyday lives and many of which pose significant risks to humans and the environment. Under TSCA and the Pollution Prevention Act, the US EPA evaluates the risks from new and existing chemicals. The agency is also tasked with finding ways to prevent or reduce pollution before it gets into the environment. The Lautenberg Chemical Safety Act gives EPA an authority to protect Americans from adverse health effects of dangerous chemicals.
Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) https://www.niehs.nih.gov/health/materials/interagency_coordinating_ committee_on_the_validation_of_alternative_methods_508.pdf Presently, the bulk of methods for assessing the potential hazards of chemicals uses laboratory animals. Alternative test methods are being developed to replace or reduce the use of animals or refine animal use to enhance animal well-being and avoid pain and distress. The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) is made up of 16 US federal research and regulatory agencies that work together to promote acceptance of these alternative tests. ICCVAM reviews and makes recommendations on new testing methods and ensures that their ability to detect potential harm is at least equal to that of current tests. ICCVAM is supported by the National Toxicology Program Interagency Center for the Evaluation of Alternative
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Toxicological Methods (NICEATM). The European Union counter partner to ICCVAM is the European Centre for the Validation of Alternative Methods (ECVAM), one of the five units in the Institute for Health and Consumer Protection (IHCP) in Ispra, Italy.
Research and nonprofit organizations National Institute of Environmental Health Sciences (NIEHS) https://www.niehs.nih.gov/index.cfm The NIEHS website states that “the mission of the National Institute of Environmental Health Sciences is to discover how the environment affects people in order to promote healthier lives.” To achieve its goals, the NIEHS depends on a set of core values that apply to all activities of the institute performs. NIEHS funds cutting edge research, training and community engagement, outreach, education, and involvement. NIEHS uses a unique form of public service to generate scientific knowledge that promotes individual and public health. The institute fosters research on environmental triggers of disease, communicates advances in environmental health sciences to the public, provides training and development of emerging young environmental health scientists and practitioners, translates knowledge from research to disease prevention, and supports safety assessment research on chemicals and other environmental factors.
National Toxicology Program (NTP) https://ntp.niehs.nih.gov/about/index.html As a division of the NIEHS, the NTP states “our vision is to maintain an objective, science-based approach to deal with critical issues in toxicology by using the best science available for our studies.” As the primary source of toxicology information for the Federal Government, NTP participates in the development of new technologies and uses the most advanced technologies available in its research. NTP does this by research and testing the potential toxicity of various substances and environmental agents, and providing that information for use in decision-making.
National Center for Toxicological Research (NCTR) https://www.federallabs.org/labs/national-center-for-toxicological-research-nctr The mission of the NCTR is to conduct peer-reviewed scientific research that supports and anticipates the FDA’s current and future regulatory needs. This involves fundamental and applied research specifically designed to define biological mechanisms of action underlying the toxicity of products regulated by the FDA. This research is aimed at understanding critical biological events in the expression of toxicity and at developing methods to improve assessment of human exposure, susceptibility, and risk.
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International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human se (ICH) https://www.ich.org The ICH is an international nonprofit association that brings together regulatory authorities and the pharmaceutical industry to discuss scientific and technical aspects of pharmaceutical product development and registration. Its mission is “to achieve greater harmonization worldwide to ensure that safe, effective, and high quality medicines are developed and registered in the most resource-efficient manner.” ICH expert working groups have developed many technical guidelines and requirements for development and registration of pharmaceutical products. The ICH guidelines are divided into four categories: quality, safety, efficacy, and multidisciplinary guidelines. Although ICH guidelines are not mandatory, toxicologists working in the pharmaceutical industry around the globe follow these guidelines during the drug development process.
International Life Sciences Institute/Health and Environmental Sciences Institute (ILSI/HESI) https://ilsi.org https://hesiglobal.org/# ILSI is a nonprofit worldwide organization that seeks to provide science that improves human health and well-being and safeguards the environment. ILSI believes scientists from industry, government, academia, and other sectors of society should work together to identify and address topics of common interest. All ILSI activities are conducted in an open and transparent manner, and all scientific outcomes are made available to the public to ensure confidence in the integrity of the scientific process. ILSI does not conduct lobbying activities, or make policy recommendations. The mission of HESI is to identify and help to resolve global health and environmental challenges through engagement of scientists from academia, government, industry, clinical practice, research institutes, and nongovernmental organizations (NGOs). HESI seeks to create a knowledge base that can be easily transferred from the laboratory or journal page to real life. Areas of scientific focus span from basic research to applied decision-frameworks in the areas of food safety, medicines, risk assessment, environmental quality, and sustainability.
Alternative Testing methods TOX21 https://www.niehs.nih.gov/research/programs/tox21/index.cfm The Toxicology in the 21st Century (Tox21) program is an ongoing collaboration among US federal agencies to characterize the potential toxicity of chemicals using cells and isolated molecular targets instead of laboratory animals.
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Tox21 leverages the experimental toxicology expertise of (1) the National Toxicology Program, headquartered at the NIEHS; (2) the high-throughput technology of the NIH Chemical Genomics Center, part of the National Center for Advancing Translational Sciences; and (3) the computational capabilities of the EPA and the expertise of the FDA. The TOX21 program has tested more than 10,000 drugs and chemical using various biological assays.
TOXCAST https://www.epa.gov/chemical-research/toxicity-forecasting The US EPA’s Toxicity Forecaster (ToxCast) generates data and predictive models on thousands of chemicals of interest. ToxCast uses state of the highthroughput screening methods and computational toxicology approaches to prioritize chemicals. ToxCast has data on approximately 1800 chemicals from a broad range of sources including industrial and consumer products. ToxCast screens chemicals in more than 700 high-throughput assay endpoints that cover a range of high-level cell responses. As EPA’s contribution partnership to Toxicology in the 21st Century federal agency collaboration, ToxCast gathers and shares its chemical data in open and transparent ways that are available to the public. National Center for Advancing Translational Sciences (NCATS) https://ncats.nih.gov NCATS is one of the 27 institutes and centers (ICs) at the National Institutes of Health (NIH). Its goal is to transform how translational research is conducted to expedite the delivery of new treatments to patients. NCATS relies on the power of data, emerging technologies, and interdisciplinary research to develop and disseminate innovations that reduce, remove, or bypass costly and timeconsuming bottlenecks in translational research. The center conducts and supports research on both the scientific and operational aspects of translational research. The institute leads the development of new medical interventions, including drugs, diagnostics, and medical devices, for all human diseases. By emphasizing collaboration, innovation, deliverables, and team science, the center enables academic scientists, the private sector, and the nonprofit community.
Institute for In Vitro Sciences (IIVS) https://iivs.org/ Founded in 1997, IIVS is recognized as a leading provider of in vitro testing in support of toxicological safety evaluations. Rigorous scientific programs coupled with educational and outreach initiatives have established IIVS as a global leader in the advancement of alternatives to animal testing.
Information sources in toxicology While there are many journals, books, and online databases that specifically publish toxicology information and results of toxicological studies, toxicology by nature is a transdisciplinary field. Toxicologists draw information from many fields of evolving science including medicine, pharmacology, physiology, biochemistry, biology, genetics and epigenetics, chemistry, and physics. Toxicologists thus have access to a rich body of scientific literature. For this introductory book, it was not the intent of the authors to compile a comprehensive list of toxicology recourses. Rather, it was our intent to provide a selected list of useful reference texts and review articles. We also provide a list and brief description of the most common computer database systems used by toxicologists. Together, these resources should provide a good place for readers to begin more in-depth reading and research.
Primary scientific literature As in any field of science, the most reliable source of information is the published, peer-reviewed literature. These journals report the results of scientific studies performed around the world by academic, government, industry, and other nonprofit research laboratories. Before the results are accepted for publication, they must undergo a rigorous peer review process. This process is managed by the journals who appoint an editor in chief, editors, and associate editors, who are usually the leading experts in their fields. Manuscripts are submitted by authors to a journal of their choosing. The editorial team then selects appropriate experts to review the manuscript. The review process includes a detailed evaluation of the scientific methods, results, statistical validity, data interpretation, and conclusions reached by the authors. In most cases, the reviewers suggest changes and additional experiments before the manuscript can be considered for publication. Manuscripts are also ranked on appropriateness for the journal, quality of the science relative to published papers, and impact on the field. Once reviewers recommend publication, the editorial team will make a final decision on whether or not to publish the manuscript. This scientific process has been sustained for hundreds of years and is self-correcting. Data that were in error, or rarely fabricated by the authors, are invariably revealed, as all science builds on previous findings. Loomis’s Essentials of Toxicology. https://doi.org/10.1016/B978-0-12-815921-7.00015-6 © 2020 Elsevier Inc. All rights reserved.
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The primary literature now comprises almost 30,000 scientific journals that are generally published on a weekly or monthly basis. One estimate puts the number of scientific papers published annually at 1.8 million. Fortunately, publishers have migrated to online publication over the last two decades. Access to the scientific literature databases allows almost instantaneous searching for all papers on a given topic from any computer. Many journals are no longer published as hard copies that sit on library shelves collecting dust. There has also been a move toward open access journals. While traditional publishers only provide access to individual researchers or libraries that pay a subscription fee, open access journals allow access to all investigators free of charge. Costs are offset by charging the authors a substantial publication fee. Given the value of open access to rapidly and widely distributing scientific findings, most traditional publishers now used a mixed model that gives the option of publishing papers as open access. Unfortunately, the popularity of open access and the lucrative nature of publishing for a fee have spawned thousands of new journals. An increasing number of these do not adhere to the ethical and expected standards of scientific publication, publishing essentially all papers submitted. This does not say that all open access journals are unreliable. Readers can usually avoid these predatory journals by referencing papers published in journals with editorial boards composed of renowned scientific leaders, those whose published impact factors that are robust, and those associated with profession scientific societies.
Secondary sources of information In addition to the primary literature, there exists a vast body of information in the form of textbooks, review articles, special reports, monographs, opinion pieces such as letters to the editors, handbooks, and a compendium of electronic databases. These secondary resources do not create scientific information; rather, they are mechanisms for locating, referencing, organizing, systematizing, condensing, abstracting, or reviewing the primary journal literature. Each is a product of a third party and therefore subject to errors of omission and commission. They are a starting point for retrieving scientific facts from peerreviewed sources. It is therefore important for students and investigators to verify crucial facts by reading the original sources in the primary journal literature. These secondary sources have the advantage that the authors have already considered a large fragment of the primary literature, including existing controversies. Considering whenever a search of the primary literature is conducted, the investigator will become aware of apparent conflicts in opinions or conclusions. This condition can be confusing to a new investigator. Often, the original sources of data as reported in the primary literature do not conflict; rather, differences are due to interpretation and extrapolation of data without proper precautions. In other instances, discrepancies can often be explained by variations in study design or experimental parameters. This is usually brought to light and
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discussed in well-written secondary publications. Thus, an additional advantage of beginning a literature review by reading the secondary literature is that they usually address discrepancies, controversies, and differences of opinion. These insights will allow readers to select the most appropriate studies and data for further investigation.
Compendia of toxicology resources The cornucopia of toxicology resources available in print and online has become almost overwhelming to those new to the field and seasoned veterans. When information is sought, it is often difficult to decide where to begin the search. In the 21st century, this usually means doing an internet-based search using one of the many powerful search engines available to everyone. However, internet search can return thousands of results, especially if the search terms are not specific, or the investigator is not sure of the right question. Fortunately, Philip Wexler took on the herculean task of putting together a compendium of information available to toxicologists in 1982. Since then, he has assumed the daunting task of editing three updated editions. The most recent one is as follows: Information Resources in Toxicology, 4th Edition Editor in chief: Philip Wexler Editors: P.J. Hakkinen, Asish Mohapatra, and Steven G. Gilbert eBook ISBN: 9780080920030 Hardcover ISBN: 9780123735935 Imprint: Academic Press Published date: July 16, 2009 Page count: 1552 This book is a sourcebook for readers who need to know where to find toxicology information. This newest edition includes extensive itemization, review, and commentary on the information infrastructure of the field. This version provides a wide-ranging, international, annotated bibliography, and compendium of major resources in toxicology and the related fields of environmental and occupational health, chemical safety, and risk assessment. The updated edition analyzes technological changes and is replete with online tools and links (URLs) to relevant web sites. The book uses a highly structured format that facilities access to information. Among the topics covered are disaster preparedness and management; omics; risk assessment; nanotechnology; the precautionary principle; and biological, chemical, and radioactive terrorism and warfare. This book is available in an inexpensive online (eBook) version. In addition, the National Institutes of Health has created the National Library of Medicine, which compiles a comprehensive list of all papers published by its grant awardees free of charge to researchers, in many cases before the journals release the papers.
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Books General toxicology Hayes’s Principles and Methods of Toxicology, 6th Edition Editors: A. Wallace Hayes and Claire L. Kruger ISBN: 978-1,842,145,364 Publisher: Taylor and Francis Published date: 09/05/2014 Page count: 2184 Casarett and Doull’s Toxicology. The Basic Science of Poisons, 9th Edition Editor: Curtis C, Klaassen ISBN: 978-1,259,863,745 Publisher: McGraw Hill Medical Published Date: November 19, 2018 Page count: 1600 Goodman and Gilman’s Pharmacological Basis of Therapeutics, 13th Edition Editors: Lawrence L. Brunton, Bjorn Knollman, and Randa Hilal-Dandan ISBN: 978-1,259,584,749 Publisher: McGraw Hill Professional Published date: October 26, 2017 Page count: 1440
Clinical toxicology Goldfrank’s Toxicologic Emergencies Editors: Lewis S. Nelson, Mary Ann Howland, Neal A. Lewin, Silas W. Smith, Lewis R. Goldfrank, and Robert S. Hoffman eBook ISBN: 978-1,259,859,618 Hardcover ISBN: 978-1,259,859,618 Publisher: McGraw Hill Education Published date: 2019 Page count: 1552 Haddad and J. F. Winchester Management of Drug Overdose, 4th Edition Editors: Michael W. Shannon, Stephen W. Borron, and Michael J. Burns ISBN: 978-0721606934 Publisher: Saunders Published date: 2007 Page count: 1584
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Industrial toxicology 2019 Threshold Limit Values and Biological Exposure Indices Editor: American Conference of Governmental Industrial Hygienists, Inc. ISBN: 978-1,607,261,056 Publisher: Signature Publications Published date: 2019 Page count: 304 Also see: https://www.chemsafetypro.com/Topics/USA/ACGIH_TLVs_ Threshold_Limit_Values.html
Risk assessment Toxicological Risk Assessment for Beginners Editors: Jose A. Torres and Sol Bobst ISBN: 978-3,319,127,507 Publisher: Springer Published date: 2015 Page count: 250 Environmental Risk Assessment: A Toxicological Approach Editor: Ted Simon ISBN: 978-1,138,033,832 Publisher: Routledge Published date: 2016 Page count: 414
Toxicogenomics Handbook of Toxicogenomics: Strategies and Applications Editor: J€ urgen Borlak ISBN: 978-3,527,604,517 Publisher: John Wiley & Sons Published date: March 6, 2006 Page count: 705 Toxicogenomics: Principles and Applications Editors: Hisham K. Hamadeh and Cynthia A. Afshari ISBN: 978-0471434177 Publisher: Wiley Published date: September 2004 Page count: 361
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Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment Authors: Committee on Applications of Toxicogenomic Technologies to Predictive Toxicology Editors: National Research Council, Division on Earth and Life Studies, Board on Life Sciences, Board on Environmental Studies and Toxicology ISBN: 978-0309112987 Publisher: National Academies Press Published date: November 19, 2007 Page count: 300 Internet Access to the National Library of Medicine’s Toxicology and Environmental Health Databases Editors: Catharyn T. Liverman, Carolyn E. Fulco, and Howard M. Kipen ISBN: 0-309-06299-3 Publisher: National Academies Press Published date: 1998 Page count: 35
Alternative methods in toxicity testing Toxicity Testing in the 21st Century. A Vision and a Strategy Authors: Committee on Toxicity Testing and Assessment of Environmental Agents Editors: Board on Environmental Studies and Toxicology Institute for Laboratory Animal Research Division on Earth and Life Studies National Research Council of the National Academies ISBN: 978-0309109925 Publisher: National Academies Press Published date: June 12, 2007 Page count: 216
Database systems POISINDEX https://truvenhealth.com/Portals/0/Assets/Brochures/International/INTL_ 12339_0614_Poisindex_A4_WEB1.pdf As part of the Micromedex Toxicology Management Solution from Truven Health Analytics, the Micromedex POISINDEX System is a reliable, evidencebased resource for identification, management, and treatment of toxic exposures. POISINDEX provides instant access to ingredient and toxic substance information on 350,000 + commercial products, chemicals, drugs, toxic plants, and animals. ToxIndex is the only system that links to other information systems such as the following: Hazardtext for hazardous compounds for incidents such as spills, leaks, fires, or explosives involving hazardous
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materials and Meditext for acute exposures to industrial chemicals. This unique capability makes POISINDEX the preferred reference of emergency first responders.
POISON CONTROL CENTERS https://aapcc.org Poison Help: 1-800-222-1222
NATIONAL LIBRARY OF MEDICINE https://www.nlm.nih.gov/about/index.html The National Library of Medicine (NLM) was founded in 1836 by National Institutes of Health in Bethesda, Maryland. NLM is the world’s largest biomedical library with an extensive collection in print. The NLM also produces electronic information resources on a wide range of topics that are searched billions of times each year by millions of people from around the world. In addition, the library coordinates a 6500-member National Network of Libraries of Medicine that promotes and provides access to health information in communities across the United States. The NLM compiles a complete list of all papers published by its grant awardees in an open access, in many cases before the journals release the papers to researchers free of charge.
TOXLINE https://toxnet.nlm.nih.gov/newtoxnet/toxline.htm Toxicology Information Online (TOXLINE) was established by the Toxicology Information Program of the NLM. It consists of a vast collection of bibliographic files containing millions of citations on virtually all aspects of toxicology. TOXLINE is a bibliographic database with citations from a wide variety of specialized journals and other sources. The database includes publications from the fields of biochemical, pharmacological, physiological, and toxicological effects of drugs and chemicals. Most of citations include abstracts and/or indexing terms and Chemical Abstract Service (CAS) Registry Numbers. TOXLINE includes references beginning in the 1840s to the present and is updated weekly.
TOXNET https://toxnet.nlm.nih.gov Toxicology Data Network (TOXNET) is produced by the Toxicology Information Program of the NLM. The database provides access to Hazardous Substances Data Bank (HSDB) Information Sources in Toxicology, Registry of Toxic Effects of Chemical Substances (RTECS), Chemical Carcinogenesis Research Information System (CCRIS), Environmental Teratology Information
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Center Backfile (ETICBACK), Environmental Mutagenesis Information Center Backfile (EMICBACK), Directory of Biotechnology Information Resources (DBIR), Toxic Chemical Release Inventory (TRI), Developmental and Reproductive Toxicology file (DART), Genetic Toxicology (GENETOX) database, and the EPA Integrated Risk Information System (IRIS). TOXNET also permits the user to create and maintain chemical records online and allows interactive review and editing of data records.
Computational Resources for Quantitative Structure-Activity Relationships (QSAR) http://crdd.osdd.net/qsar.php http://vega.marionegri.it/wordpress/wp-content/uploads/2011/09/chap8.pdf Quantitative structural-activity relationship (QSAR) quantitatively correlates the structure of molecule (descriptors) with their physicochemical properties, biological activities, and toxicity. The method uses statistical analyses (e.g., multiple linear regression, partial least square, support vector machines, artificial neural network, decision trees, and Bayesian classifier) to generate mathematical models that relate a set of chemical descriptors to experimentally measured parameters. QSAR models are then used to predict biological activities and undesired effects of untested or novel compounds and to provide insight into relevant and consistent chemical properties or structural features that define biological activity. Once a series of predicted models are collected, QSAR can also be used to mine database to identify candidate compounds with specific biological activities, particularly, for those having drug-like properties and suitable pharmacokinetic properties.
The OECD QSAR Toolbox http://www.oecd.org/chemicalsafety/risk-assessment/oecd-qsar-toolbox.htm To increase the regulatory acceptance of (Q)SAR methods, the Organization for Economic Cooperation and Development (OECD) has developed a QSAR Toolbox to make (Q)SAR technology readily accessible, transparent, and less expensive. The toolbox provides a robust compilation of software, databases, websites for QSARs and for the European Union’s Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH).
PUBMED https://www.nlm.nih.gov/bsd/pubmed.html PUBMED is a free resource developed and maintained by the National Center for Biotechnology Information (NCBI) at the NLM. PubMed provides free access to Medline; NLM’s database of citations; and abstracts in the fields of medicine, nursing, dentistry, veterinary medicine, health care systems, and preclinical sciences. The database also includes citations to some additional
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life science journals that submit full-text articles to PUBMED Central and receive a qualitative review by NLM. The resource has citations for the majority of books and book chapters available on the NCBI Bookshelf. Links to full-text articles are found in PUBMED Central or at publisher web sites. The recourse also provides advanced search, clinical queries search filters, and special queries pages. PUBMED includes discovery tools to find related papers of interest and provides links to NCBI molecular biology resources. The database is updated daily.
Medical Information online (MEDLINE) https://www.nlm.nih.gov/bsd/medline.html MEDLINE is the NLM’s most extensive bibliographic database. The database contains more than 25 million references to journal articles primarily in the life sciences. MEDLINE records are indexed with NLM Medical Subject Headings (MeSH). MEDLINE is the online version to MEDical Literature Analysis and Retrieval System (MEDLARS) that was initiated in 1964. MEDLINE is the primary component of PUBMED, part of the Entrez series of databases provided by the NCBI. The database includes publications from 1966 to present, with limited coverage prior to that period. Citations are compiled from more than 5200 worldwide journals in about 40 languages. Citations are added to PubMed 7 days a week. More than 904,636 citations were added to MEDLINE in 2018. On their web page, MEDLINE indicates that the subject scope of their database is “biomedicine and health, broadly defined to encompass those areas of the life sciences; behavioral sciences; chemical sciences; and bioengineering needed by health professionals and others engaged in basic research and clinical care, public health, health policy development, or related educational activities. MEDLINE also covers life sciences vital to biomedical practitioners, researchers, and educators, including aspects of biology, environmental science, marine biology, plant and animal science, and biophysics and chemistry.”
BIOSIS https://clarivate.libguides.com/webofscienceplatform/bci https://clarivate.libguides.com/webofscienceplatform/introduction BIOSIS Citation Index is part of the Web of Science, a platform consisting of literature search databases designed to support scientific and scholarly research. BIOSIS combines indexed life science coverage found in BIOSIS Previews (biological abstracts, reports, reviews, and meetings) with searching tools for references in 5300 journals and over 165,000 items from more than 1500 meetings (1926–present). Subject coverage includes traditional areas of biology like botany, zoology, and microbiology. Interdisciplinary areas of science including agriculture, biochemistry, bioengineering, biomedical, biophysics, biotechnology, ecology, medicine, and pharmacology are also covered.
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International Pharmaceutical Abstracts https://health.ebsco.com/products/international-pharmaceutical-abstracts Produced by Clarivate Analytics, this database provides extensive indexing and abstracts for pharmaceutical and medical journals published worldwide. The database includes more than 500,000 abstracted and indexed records from more than 800 global journals dating back to 1970. Subjects covered include biopharmaceuticals and pharmacokinetics; legal, political, and ethical issues; new drug delivery systems; and pharmacist liability.
Government and regulatory agencies Organization for Economic Cooperation and Development (OECD) https://www.oecd.org/about/ The mission of the OECD is to promote policies that can improve the economic and social well-being of people around the world. The OECD was established in 1960s when 18 European countries plus the United States and Canada joined forces to create an organization. Today, the OECD is a group of 36 member countries around the globe that discuss and develop economic and social policies. The OECD provides a forum for governments to cooperate, share experiences, and seek solutions to common problems. OECD sets international standards on a wide range of matters from agriculture and taxes to the safety of chemicals.
USA Food and Drug Administration (FDA) https://www.fda.gov https://open.fda.gov/ The FDA is a federal agency of the US Department of Health and Human Services. The FDA is responsible for protecting public health through the regulations of food safety, dietary supplements, prescription and over-the-counter (OTC) medications, vaccines, biologics, blood transfusions, medical devices, electromagnetic radiation-emitting devices, cosmetics, tobacco products, animal food, and veterinary products. FDA scientific committees provide evidence-based recommendations on medicines for human and veterinary use and other areas of regulatory interest to the agency. The agency provides marketing authorization and monitors veracity of advertising and postmarketing pharmacovigilance. The agency also coordinates inspections in connection with the assessment of marketing authorization applications or matters referred to its committees. The FDA has collected a large amount of data through the decades. In 2013, OpenFDA was created to enable the public to have easy access to such data. The ultimate goal of data sharing is to educate people and save lives.
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European Medical Agency (EMA) https://www.ema.europa.eu The mission of the EMA is to foster scientific excellence in the evaluation and supervision of medicines for the benefit of public and animal health in the European Union (EU). EMA is the European counterpart of the US FDA. EMA enables timely development and patient access to new medicines for the benefit of patients. The agency also supports research and innovation in the pharmaceutical sector and promotes innovation and development of new medicines. EMA’s scientific committees provide evidence-based recommendations on medicines for human and veterinary use. The agency’s evaluation of marketing authorization is the basis for the authorization of medicines in the European Union. EMA also coordinates inspections in connection with the assessment of marketing authorization applications. EMA continuously monitors and supervises the safety of medicines that have been authorized in the EU to ensure that their benefits outweigh their risks. The agency also monitors industry compliance with their pharmacovigilance obligations.
Registration, Evaluation, Authorization and Restriction of Chemicals (REACH), European Union http://ec.europa.eu/environment/chemicals/reach/background/index_en.htm The goal of REACH (EC 1907/2006) is to improve protection of human health and the environment through early identification of the intrinsic hazard of chemicals. REACH meets these goals through registration, evaluation, authorization, and restriction of chemicals. REACH also seeks to enhance innovation and competitiveness in the EU chemical industry via the “No data, no market” rule. REACH places responsibility for managing risks from chemical exposures in industries and provides safety information on the substances. Manufacturers and importers must gather information on the properties of chemical substances to ensure safe handling. They are also required to register the information in a central database in the European Chemicals Agency (ECHA) in Helsinki, Finland. ECHA manages the necessary database systems, coordinates evaluation of suspicious chemicals, and provides a public database in which consumers and professionals can find hazard information. Reach also calls for the progressive substitution of the most dangerous chemicals (referred to as “substances of very high concern”) with suitable alternatives.
Agency for Toxic Substances and Disease Registry (ATSDR) https://www.atsdr.cdc.gov The registry (ATSDR) is a federal public health agency within the US Department of Health and Human Services. The mission of the agency is to protect communities from harmful health effects related to exposure to natural and
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man-made hazardous substances. ATSDR responds to environmental health emergencies, investigates emerging environmental health threats, conducts research on the health impacts of hazardous waste sites, and provides actionable guidance to state and local health partners.
US Environmental Protection Agency (EPA) https://www.epa.gov The mission of the EPA is to protect human health and the environment. The EPA is responsible for environmental stewardship and ensures that Americans have clean air, land, and water. The agency’s leading efforts to reduce environmental risks are based on the best available scientific information. The EPA enforces Federal laws to protect human health and the environment communities. The EPA oversees the cleanup of contaminated lands and toxic sites. The EPA works with businesses, nonprofit organizations, and state and local governments through partnerships on conserving water and energy, minimizing greenhouse gases, reusing solid waste, and getting a handle on pesticide risks. The EPA shares information and publicly recognizes its partners.
Integrated Risk Information System (IRIS) https://www.epa.gov/iris EPA’s IRIS program supports EPA’s mission by identifying and characterizing the health hazards of chemicals found in the environment. Each IRIS assessment can cover a chemical, a group of related chemicals, or a complex mixture. IRIS assessments determine the following toxicity values for health effects resulting from chronic exposure to chemicals: (1) reference Dose (RfD), an estimated daily oral exposure to the human population that is likely to be without an appreciable risk of deleterious effects during a lifetime; (2) reference Concentration (RfC), an estimated daily exposure by inhalation that is likely to be without an appreciable risk of deleterious effects during a lifetime; (3) cancer descriptors; (4) oral slope factor (OSF), an estimate of the increased cancer risk from oral exposure to a dose of 1 mg/kg/day for a lifetime; and (5) inhalation unit risk (IUR), an estimate of the increased cancer risk from inhalation exposure to a concentration of 1 μg/m3 for a lifetime.
Occupational Safety and Health Administration (OSHA) https://www.osha.gov/about.html OSHA is part of the US Department of Labor. The US Congress created OSHA in 1970 to ensure safer and healthy working environments for working men and women. OSHA sets and enforces standards and provides training, outreach, education, and assistance. The OSH Act covers most private sector employers and their workers, some public sector employers and workers in
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the 50 states and certain territories, and jurisdictions under federal authority including the District of Columbia, Puerto Rico, the Virgin Islands, American Samoa, Guam, Northern Mariana Islands, Wake Island, Johnston Island, and the Outer Continental Shelf Lands as defined in the Outer Continental Shelf Lands Act.
The National Institute for Occupational Safety and Health (NIOSH) https://www.cdc.gov/niosh/about/default.html https://www.aiha.org/Pages/default.aspx Under the jurisdiction of the Centers for Disease Control and Prevention, NIOSH develops and translates new knowledge in the field of occupational safety and health. NIOSH seeks to reduce worker illness and injury and to advance worker well-being by tracking work-related hazards, exposures, illnesses, and injuries for prevention. NIOSH promotes safe and healthy workers through research interventions, recommendations, capacity building and global collaborations.
Toxic Substances Control Act (TSCA) https://www.epa.gov/chemicals-under-tsca Chemicals regulated by TSCA include many products that we use in our everyday lives and many of which pose significant risks to humans and the environment. Under TSCA and the Pollution Prevention Act, the US EPA evaluates the risks from new and existing chemicals. The agency is also tasked with finding ways to prevent or reduce pollution before it gets into the environment. The Lautenberg Chemical Safety Act gives EPA an authority to protect Americans from adverse health effects of dangerous chemicals.
Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) https://www.niehs.nih.gov/health/materials/interagency_coordinating_ committee_on_the_validation_of_alternative_methods_508.pdf Presently, the bulk of methods for assessing the potential hazards of chemicals uses laboratory animals. Alternative test methods are being developed to replace or reduce the use of animals or refine animal use to enhance animal well-being and avoid pain and distress. The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) is made up of 16 US federal research and regulatory agencies that work together to promote acceptance of these alternative tests. ICCVAM reviews and makes recommendations on new testing methods and ensures that their ability to detect potential harm is at least equal to that of current tests. ICCVAM is supported by the National Toxicology Program Interagency Center for the Evaluation of Alternative
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Toxicological Methods (NICEATM). The European Union counter partner to ICCVAM is the European Centre for the Validation of Alternative Methods (ECVAM), one of the five units in the Institute for Health and Consumer Protection (IHCP) in Ispra, Italy.
Research and nonprofit organizations National Institute of Environmental Health Sciences (NIEHS) https://www.niehs.nih.gov/index.cfm The NIEHS website states that “the mission of the National Institute of Environmental Health Sciences is to discover how the environment affects people in order to promote healthier lives.” To achieve its goals, the NIEHS depends on a set of core values that apply to all activities of the institute performs. NIEHS funds cutting edge research, training and community engagement, outreach, education, and involvement. NIEHS uses a unique form of public service to generate scientific knowledge that promotes individual and public health. The institute fosters research on environmental triggers of disease, communicates advances in environmental health sciences to the public, provides training and development of emerging young environmental health scientists and practitioners, translates knowledge from research to disease prevention, and supports safety assessment research on chemicals and other environmental factors.
National Toxicology Program (NTP) https://ntp.niehs.nih.gov/about/index.html As a division of the NIEHS, the NTP states “our vision is to maintain an objective, science-based approach to deal with critical issues in toxicology by using the best science available for our studies.” As the primary source of toxicology information for the Federal Government, NTP participates in the development of new technologies and uses the most advanced technologies available in its research. NTP does this by research and testing the potential toxicity of various substances and environmental agents, and providing that information for use in decision-making.
National Center for Toxicological Research (NCTR) https://www.federallabs.org/labs/national-center-for-toxicological-research-nctr The mission of the NCTR is to conduct peer-reviewed scientific research that supports and anticipates the FDA’s current and future regulatory needs. This involves fundamental and applied research specifically designed to define biological mechanisms of action underlying the toxicity of products regulated by the FDA. This research is aimed at understanding critical biological events in the expression of toxicity and at developing methods to improve assessment of human exposure, susceptibility, and risk.
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International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human se (ICH) https://www.ich.org The ICH is an international nonprofit association that brings together regulatory authorities and the pharmaceutical industry to discuss scientific and technical aspects of pharmaceutical product development and registration. Its mission is “to achieve greater harmonization worldwide to ensure that safe, effective, and high quality medicines are developed and registered in the most resource-efficient manner.” ICH expert working groups have developed many technical guidelines and requirements for development and registration of pharmaceutical products. The ICH guidelines are divided into four categories: quality, safety, efficacy, and multidisciplinary guidelines. Although ICH guidelines are not mandatory, toxicologists working in the pharmaceutical industry around the globe follow these guidelines during the drug development process.
International Life Sciences Institute/Health and Environmental Sciences Institute (ILSI/HESI) https://ilsi.org https://hesiglobal.org/# ILSI is a nonprofit worldwide organization that seeks to provide science that improves human health and well-being and safeguards the environment. ILSI believes scientists from industry, government, academia, and other sectors of society should work together to identify and address topics of common interest. All ILSI activities are conducted in an open and transparent manner, and all scientific outcomes are made available to the public to ensure confidence in the integrity of the scientific process. ILSI does not conduct lobbying activities, or make policy recommendations. The mission of HESI is to identify and help to resolve global health and environmental challenges through engagement of scientists from academia, government, industry, clinical practice, research institutes, and nongovernmental organizations (NGOs). HESI seeks to create a knowledge base that can be easily transferred from the laboratory or journal page to real life. Areas of scientific focus span from basic research to applied decision-frameworks in the areas of food safety, medicines, risk assessment, environmental quality, and sustainability.
Alternative Testing methods TOX21 https://www.niehs.nih.gov/research/programs/tox21/index.cfm The Toxicology in the 21st Century (Tox21) program is an ongoing collaboration among US federal agencies to characterize the potential toxicity of chemicals using cells and isolated molecular targets instead of laboratory animals.
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Tox21 leverages the experimental toxicology expertise of (1) the National Toxicology Program, headquartered at the NIEHS; (2) the high-throughput technology of the NIH Chemical Genomics Center, part of the National Center for Advancing Translational Sciences; and (3) the computational capabilities of the EPA and the expertise of the FDA. The TOX21 program has tested more than 10,000 drugs and chemical using various biological assays.
TOXCAST https://www.epa.gov/chemical-research/toxicity-forecasting The US EPA’s Toxicity Forecaster (ToxCast) generates data and predictive models on thousands of chemicals of interest. ToxCast uses state of the highthroughput screening methods and computational toxicology approaches to prioritize chemicals. ToxCast has data on approximately 1800 chemicals from a broad range of sources including industrial and consumer products. ToxCast screens chemicals in more than 700 high-throughput assay endpoints that cover a range of high-level cell responses. As EPA’s contribution partnership to Toxicology in the 21st Century federal agency collaboration, ToxCast gathers and shares its chemical data in open and transparent ways that are available to the public. National Center for Advancing Translational Sciences (NCATS) https://ncats.nih.gov NCATS is one of the 27 institutes and centers (ICs) at the National Institutes of Health (NIH). Its goal is to transform how translational research is conducted to expedite the delivery of new treatments to patients. NCATS relies on the power of data, emerging technologies, and interdisciplinary research to develop and disseminate innovations that reduce, remove, or bypass costly and timeconsuming bottlenecks in translational research. The center conducts and supports research on both the scientific and operational aspects of translational research. The institute leads the development of new medical interventions, including drugs, diagnostics, and medical devices, for all human diseases. By emphasizing collaboration, innovation, deliverables, and team science, the center enables academic scientists, the private sector, and the nonprofit community.
Institute for In Vitro Sciences (IIVS) https://iivs.org/ Founded in 1997, IIVS is recognized as a leading provider of in vitro testing in support of toxicological safety evaluations. Rigorous scientific programs coupled with educational and outreach initiatives have established IIVS as a global leader in the advancement of alternatives to animal testing.