Biomaterial Database

Risk assessment methodology: maximum tolerated dose and two-stage carcinogenesis models. 1994

B D Goldstein

Environmental and Occupational Health Sciences Institute, Piscataway, New Jersey 08855.

The Committee on Risk Assessment Methodology of the Board on Environmental Studies and Toxicology of the National Academy of Sciences has considered issues related to the use of the maximum tolerated dose (MTD) in carcinogenesis bioassays and of 2-stage models of carcinogenesis. In each case, the goal has been to consider whether sufficient information is available to lead to a change in current methodology used by regulatory agencies in assessing risk. The majority of the committee favored retention of the MTD but recommended that lower doses also be used for cancer bioassays and, if the results are positive, performance of additional mechanistic studies aimed at improved extrapolation to environmentally relevant concentrations. The minority recommended that additional preliminary studies be done in order to obtain information about the highest dose relevant to extrapolation to humans for use in the cancer bioassay. Two-stage carcinogenesis models were found to be an excellent approach to increase understanding but required an extensive toxicological data base beyond that available for most chemicals. These deliberations have highlighted the value of increased understanding of the basic mechanisms of action of potential cancer-causing chemicals in order to advance the methodology of risk assessment.

UI	MeSH Term	Description	Entries
D008452	Maximum Allowable Concentration	The maximum exposure to a biologically active physical or chemical agent that is allowed during an 8-hour period (a workday) in a population of workers, or during a 24-hour period in the general population, which does not appear to cause appreciable harm, whether immediate or delayed for any period, in the target population. (From Lewis Dictionary of Toxicology, 1st ed)	Maximum Permissible Exposure Level,MPEL,Maximum Permissible Exposure Concentration,Allowable Concentration, Maximum,Allowable Concentrations, Maximum,Concentration, Maximum Allowable,Concentrations, Maximum Allowable,MPELs,Maximum Allowable Concentrations
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009369	Neoplasms	New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015197	Carcinogenicity Tests	Tests to experimentally measure the tumor-producing/cancer cell-producing potency of an agent by administering the agent (e.g., benzanthracenes) and observing the quantity of tumors or the cell transformation developed over a given period of time. The carcinogenicity value is usually measured as milligrams of agent administered per tumor developed. Though this test differs from the DNA-repair and bacterial microsome MUTAGENICITY TESTS, researchers often attempt to correlate the finding of carcinogenicity values and mutagenicity values.	Tumorigenicity Tests,Carcinogen Tests,Carcinogenesis Tests,Carcinogenic Activity Tests,Carcinogenic Potency Tests,Carcinogen Test,Carcinogenesis Test,Carcinogenic Activity Test,Carcinogenic Potency Test,Carcinogenicity Test,Potency Test, Carcinogenic,Potency Tests, Carcinogenic,Test, Carcinogen,Test, Carcinogenesis,Test, Carcinogenic Activity,Test, Carcinogenic Potency,Test, Carcinogenicity,Test, Tumorigenicity,Tests, Carcinogen,Tests, Carcinogenesis,Tests, Carcinogenic Activity,Tests, Carcinogenic Potency,Tests, Carcinogenicity,Tests, Tumorigenicity,Tumorigenicity Test
D018570	Risk Assessment	The qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences. (Last, Dictionary of Epidemiology, 1988)	Assessment, Risk,Benefit-Risk Assessment,Risk Analysis,Risk-Benefit Assessment,Health Risk Assessment,Risks and Benefits,Analysis, Risk,Assessment, Benefit-Risk,Assessment, Health Risk,Assessment, Risk-Benefit,Benefit Risk Assessment,Benefit-Risk Assessments,Benefits and Risks,Health Risk Assessments,Risk Analyses,Risk Assessment, Health,Risk Assessments,Risk Benefit Assessment,Risk-Benefit Assessments