The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) coordinates U.S. federal government evaluation of new, revised, and alternative test methods. Alternative methods are methods for safety testing of chemicals and chemical products that use fewer or no animals or that minimize or prevent animal pain and distress.
The ICCVAM Authorization Act of 2000 created ICCVAM to "establish, wherever feasible, guidelines, recommendations, and regulations that promote the regulatory acceptance of new or revised scientifically valid safety testing methods that protect human and animal health and the environment while reducing, refining, and replacing animal tests and ensuring human safety and product effectiveness". [1] This Act addressed directives in the NIH Revitalization Act of 1993 [2] requiring that the National Institute of Environmental Health Sciences (NIEHS) establish criteria for the validation and regulatory acceptance of alternative test methods. ICCVAM is a permanent interagency committee under NIEHS and receives administrative and scientific support from the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM).
ICCVAM has evaluated and developed recommendations to U.S. federal agencies on alternative tests for substances that can cause skin and eye injuries or allergic contact dermatitis, as well as non-animal tests to identify potential pyrogens and endocrine disruptors. ICCVAM has also convened workshops to facilitate acceptance and use of alternatives for vaccine testing and to assess the usefulness of aquatic models and adverse outcome pathways for high-throughput non-animal testing approaches.
ICCVAM facilitates international collaboration on the development of alternative test methods through its membership in the International Cooperation on Alternative Test Methods and ICCVAM agency participation in the Test Guidelines Programme of the Organisation for Economic Co-operation and Development.
ICCVAM produces biennial reports summarizing its activities. These reports are available on the National Toxicology Program website; the last report [3] was published in July 2014 and describes ICCVAM activities in 2012 and 2013.
ICCVAM relies on stakeholders to carry out alternative test method research, development, and validation studies. ICCVAM's stakeholders include:
ICCVAM meets 8-10 times per year. Opportunities for stakeholders to interact with committee members include:
ICCVAM reports and summaries of current ICCVAM activities are available on the National Toxicology Program website. An email list informs stakeholders of ICCVAM activities and other news of interest to developers and users of alternative test methods.
Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating exposures to toxins and toxicants. The relationship between dose and its effects on the exposed organism is of high significance in toxicology. Factors that influence chemical toxicity include the dosage, duration of exposure, route of exposure, species, age, sex, and environment. Toxicologists are experts on poisons and poisoning. There is a movement for evidence-based toxicology as part of the larger movement towards evidence-based practices. Toxicology is currently contributing to the field of cancer research, since some toxins can be used as drugs for killing tumor cells. One prime example of this is ribosome-inactivating proteins, tested in the treatment of leukemia.
The Draize test is an acute toxicity test devised in 1944 by Food and Drug Administration (FDA) toxicologists John H. Draize and Jacob M. Spines. Initially used for testing cosmetics, the procedure involves applying 0.5 mL or 0.5 g of a test substance to the eye or skin of a restrained, conscious animal, and then leaving it for set amount of time before rinsing it out and recording its effects. The animals are observed for up to 14 days for signs of erythema and edema in the skin test, and redness, swelling, discharge, ulceration, hemorrhaging, cloudiness, or blindness in the tested eye. The test subject is commonly an albino rabbit, though other species are used too, including dogs. The animals are euthanized after testing if the test renders irreversible damage to the eye or skin. Animals may be re-used for testing purposes if the product tested causes no permanent damage. Animals are typically reused after a "wash out" period during which all traces of the tested product are allowed to disperse from the test site.
In vitro toxicity testing is the scientific analysis of the toxic effects of chemical substances on cultured bacteria or mammalian cells. In vitro testing methods are employed primarily to identify potentially hazardous chemicals and/or to confirm the lack of certain toxic properties in the early stages of the development of potentially useful new substances such as therapeutic drugs, agricultural chemicals and food additives.
The Agency for Toxic Substances and Disease Registry (ATSDR) is a federal public health agency within the United States Department of Health and Human Services' Centers for Disease Control and Prevention. The agency focuses on minimizing human health risks associated with exposure to hazardous substances. It works closely with other federal, state, and local agencies; tribal governments; local communities; and healthcare providers. Its mission is to "Serve the public through responsive public health actions to promote healthy and safe environments and prevent harmful exposures." ATSDR was created as an advisory, nonregulatory agency by the Superfund legislation and was formally organized in 1985.
Aquatic toxicology is the study of the effects of manufactured chemicals and other anthropogenic and natural materials and activities on aquatic organisms at various levels of organization, from subcellular through individual organisms to communities and ecosystems. Aquatic toxicology is a multidisciplinary field which integrates toxicology, aquatic ecology and aquatic chemistry.
The National Institute of Environmental Health Sciences (NIEHS) conducts research into the effects of the environment on human disease, as one of the 27 institutes and centers of the National Institutes of Health (NIH). It is located in the Research Triangle Park in North Carolina, and is the only primary division of the NIH located outside of the Washington metropolitan area.
Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) is a European Union regulation dating from 18 December 2006. REACH addresses the production and use of chemical substances, and their potential impacts on both human health and the environment. Its 849 pages took seven years to pass, and it has been described as the most complex legislation in the Union's history and the most important in 20 years. It is the strictest law to date regulating chemical substances and will affect industries throughout the world. REACH entered into force on 1 June 2007, with a phased implementation over the next decade. The regulation also established the European Chemicals Agency, which manages the technical, scientific and administrative aspects of REACH.
Toxicogenomics is a subdiscipline of pharmacology that deals with the collection, interpretation, and storage of information about gene and protein activity within a particular cell or tissue of an organism in response to exposure to toxic substances. Toxicogenomics combines toxicology with genomics or other high-throughput molecular profiling technologies such as transcriptomics, proteomics and metabolomics. Toxicogenomics endeavors to elucidate the molecular mechanisms evolved in the expression of toxicity, and to derive molecular expression patterns that predict toxicity or the genetic susceptibility to it.
David Platt Rall was a cancer specialist and a leader in environmental health studies, whose work in environmental health helped turn it into a scientific discipline. Rall also advanced public health and prevention. He directed the National Institute of Environmental Health Sciences from 1971 to 1990, year in which he retired. His work on toxicology and carcinogenesis was recognized by his appointment as the first director of the National Toxicology Program in 1978. He held the rank of Assistant Surgeon General in the United States Public Health Service. He also chaired the World Health Organization's Program on Chemical Safety.
The National Toxicology Program (NTP) is an inter-agency program run by the United States Department of Health and Human Services to coordinate, evaluate, and report on toxicology within public agencies.
Alternatives to animal testing are the development and implementation of test methods that avoid the use of live animals. There is widespread agreement that a reduction in the number of animals used and the refinement of testing to reduce suffering should be important goals for the industries involved. Two major alternatives to in vivo animal testing are in vitro cell culture techniques and in silico computer simulation; however, some claim they are not true alternatives because simulations use data from prior animal experiments and cell cultures often require animal derived products, such as serum or cells. Others say that they cannot replace animals completely as they are unlikely to ever provide enough information about the complex interactions of living systems.
The fixed-dose procedure (FDP), proposed in 1992 by the British Toxicology Society, is a method to assess a substance's acute oral toxicity.
High production volume chemicals are produced or imported into the United States in quantities of 1 million pounds or 500 tons per year. In OECD countries, HPV chemicals are defined as being produced at levels greater than 1,000 metric tons per producer/importer per year in at least one member country/region. A list of HPV chemicals serves as an overall priority list, from which chemicals are selected to gather data for a screening information dataset (SIDS), for testing and for initial hazard assessment.
The Pest Management Regulatory Agency (PMRA) is the Canadian government agency responsible for the regulation of pest control products in Canada under the federal authority of the Pest Control Products Act and Regulations. The agency is a branch that reports to Parliament through Health Canada. The PMRA is responsible for providing access to pest management tools while minimizing the risks to human health and the environment by “using modern evidence-based scientific approaches to pesticide regulation, in an open and transparent manner”. Their main activity areas include: new product evaluation, post market review and compliance and enforcement.
Nanomaterials can be both incidental and engineered. Engineered nanomaterials (ENMs) are nanoparticles that are made for use, are defined as materials with dimensions between 1 and 100nm, for example in cosmetics or pharmaceuticals like zinc oxide and TiO2 as well as microplastics. Incidental nanomaterials are found from sources such as cigarette smoke and building demolition. Engineered nanoparticles have become increasingly important for many applications in consumer and industrial products, which has resulted in an increased presence in the environment. This proliferation has instigated a growing body of research into the effects of nanoparticles on the environment. Natural nanoparticles include particles from natural processes like dust storms, volcanic eruptions, forest fires, and ocean water evaporation.
Rise for Animals is a national, registered 501(c)(3) nonprofit animal rights organization which aims to end nonhuman animal experimentation. It has been described as "one of the oldest and wealthiest anti-vivisection organizations in the United States".
The non-profit Evidence-based Toxicology Collaboration (EBTC) comprises a group of scientists and experts with ties to governmental and non-governmental agencies, chemical and pharmaceutical companies, and academia that have banded together to promote the use of what are known as "evidence-based approaches" in toxicology. The discipline of evidence-based toxicology (EBT) is a process for transparently, consistently, and objectively assessing available scientific evidence in order to answer questions in toxicology. EBT has the potential to address concerns in the toxicological community about the limitations of current approaches. These include concerns related to transparency in decision making, synthesis of different types of evidence, and the assessment of bias and credibility. The evidence-based methods and approaches now being proposed for toxicology are widely used in medicine, which is the basis for their nomenclature. The need to improve how the performance of toxicological test methods is assessed was the main impetus for translating these tools to toxicology.
An adverse outcome pathway (AOP) is structured representation of biological events leading to adverse effects and is considered relevant to risk assessment. The AOP links in a linear way existing knowledge along one or more series of causally connected key events (KE) between two points — a molecular initiating event (MIE) and an adverse outcome (AO) that occur at a level of biological organization relevant to risk assessment. The linkage between the events is described by key event relationships (KER) that describe the causal relationships between the key events.
The German Federal Institute for Risk Assessment, abbreviated BfR, is a body under public law of the German federal government with full legal capacity. The institute comes under the portfolio of the Federal Ministry of Food and Agriculture and has the task of providing scientific advice to the federal government on issues relating to food safety, product safety, chemical safety, contaminants in the food chain, animal protection and consumer health protection. Further technical supervision is performed by the Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety and the Federal Ministry of Transport.
A bioassay is an analytical method to determine the potency or effect of a substance by its effect on living animals or plants, or on living cells or tissues. A bioassay can be either quantal or quantitative, direct or indirect. If the measured response is binary, the assay is quantal; if not, it is quantitative.