Terminology Services

Integrated Risk Information System (IRIS) Glossary

Description:

This glossary contains definitions of terms used frequently in IRIS Program assessments and related materials. These definitions assumed that the user has some familiarity with risk assessment and health science.

Publishing Organization:

Office of Research and Development/Center for Public Health and Environmental Assessment/Chemical and Pollutant Assessment Division

Last Update:

June 22, 2022

Program Site:

https://www.epa.gov/iris

Terms & Acronyms

Search Terms

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	Term
	Acceptable Daily Intake	Definition: The amount of a chemical a person can be exposed to on a daily basis over an extended period of time (usually a lifetime) without suffering deleterious effects. Acronym: ADI
	Acute Exposure	Definition: Exposure by the oral, dermal, or inhalation route for 24 hours or less.
	Acute Reference Concentration	Definition: An estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure for an acute duration (24 hours or less) to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark concentration, with uncertainty factors generally applied to reflect limitations of the data used. Generally used in EPA's noncancer health assessments. Acronym: Acute RfC
	Acute Reference Dose	Definition: An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure for an acute duration (24 hours or less) to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark dose, with uncertainty factors generally applied to reflect limitations of the data used. Generally used in EPA's noncancer health assessments. Acronym: Acute RfD
	Acute Toxicity	Definition: Any poisonous effect produced within a short period of time following an exposure, usually 24 to 96 hours.
	Added Risk	Definition: See Additional Risk.
	Additional Risk	Definition: The calculated difference in risk of a particular condition between those who are exposed and those who are not. This measure is derived by subtracting the rate (usually incidence or mortality) of the disease among the unexposed persons (Pu) from the corresponding rate among the exposed (Pe), i.e., AR= Pe-Pu. The AR is an absolute measure of the excess risk attributed to exposure. Acronym: AR
	Adverse Effect	Definition: A biochemical change, functional impairment, or pathologic lesion that affects the performance of the whole organism, or reduces an organism's ability to respond to an additional environmental challenge.
	Aerodynamic Diameter	Definition: The diameter of a sphere with unit density that has aerodynamic behavior identical to that of the particle in question; an expression of aerodynamic behavior of an irregularly shaped particle in terms of the diameter of an idealized particle. Particles having the same aerodynamic diameter may have different dimensions and shapes.
	Aerosol	Definition: A suspension of liquid or solid particles in air.
	Anecdotal Data	Definition: Data based on the description of individual cases rather than controlled studies.
	Attributable Risk	Definition: See Additional Risk.
	Average Daily Dose	Definition: Dose rate averaged over a pathway-specific period of exposure expressed as a daily dose on a per-unit-body-weight basis. The ADD is usually expressed in terms of mg/kg-day or other mass-time units. Acronym: ADD
	Background Levels	Definition: Two types of background levels may exist for chemical substances: (a) Naturally occurring levels: Ambient concentrations of substances present in the environment, without human influence; (b) Anthropogenic levels: Concentrations of substances present in the environment due to human-made, non-site sources (e.g., automobiles, industries).
	Benchmark Concentration	Definition: A dose or concentration that produces a predetermined change in response rate of an adverse effect (called the benchmark response or BMR) compared to background. Acronym: BMC
	Benchmark Dose	Definition: A dose or concentration that produces a predetermined change in response rate of an adverse effect (called the benchmark response or BMR) compared to background. Acronym: BMD
	Benchmark Response	Definition: An adverse effect, used to define a benchmark dose from which an RfD (or RfC) can be developed. The change in response rate over background of the BMR is usually in the range of 5-10%, which is the limit of responses typically observed in well-conducted animal experiments. Acronym: BMR
	Benign Tumor	Definition: A tumor that does not spread to a secondary localization, but may impair normal biological function through obstruction or may progress to malignancy later.
	Bioassay	Definition: An assay for determining the potency (or concentration) of a substance that causes a biological change in experimental animals.
	Bioavailability	Definition: The degree to which a substance becomes available to the target tissue after administration or exposure.
	Biologically Based Dose Response Model	Definition: A predictive model that describes biological processes at the cellular and molecular level linking the target organ dose to the adverse effect. Acronym: BBDR Model
	Blood to Air Partition Coefficient	Definition: A ratio of a chemical's concentration between blood and air when at equilibrium.
	BMCL	Definition: A statistical lower confidence limit on the dose or concentration at the BMD or BMC, respectively.
	BMDL	Definition: A statistical lower confidence limit on the dose or concentration at the BMD or BMC, respectively.
	Cancer	Definition: A disease of heritable, somatic mutations affecting cell growth and differentiation, characterized by an abnormal, uncontrolled growth of cells.
	Carcinogen	Definition: An agent capable of inducing cancer.
	Carcinogenesis	Definition: The origin or production of a benign or malignant tumor. The carcinogenic event modifies the genome and/or other molecular control mechanisms of the target cells, giving rise to a population of altered cells.
	CAS Registry Number	Definition: The Chemical Abstract Service Registry Number (CASRN) is an unique numeric identifier, designed to designate only one substance so it can be referenced by many Government Agencies and/or internationally. Acronym: CASRN
	Case-control Study	Definition: An epidemiologic study contrasting those with the disease of interest (cases) to those without the disease (controls). The groups are then compared with respect to exposure history, to ascertain whether they differ in the proportion exposed to the chemical(s) under investigation.
	Chronic Effect	Definition: An effect that occurs as a result of repeated or long term (chronic) exposures.
	Chronic Exposure	Definition: Repeated exposure by the oral, dermal, or inhalation route for more than approximately 10% of the life span in humans (more than approximately 90 days to 2 years in typically used laboratory animal species).
	Chronic Reference Concentration	Definition: An estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure for a chronic duration (up to a lifetime) to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark concentration, with uncertainty factors generally applied to reflect limitations of the data used. Generally used in EPA's noncancer health assessments. Acronym: Chronic RfC
	Chronic Reference Dose	Definition: An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure for a chronic duration (up to a lifetime) to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark dose, with uncertainty factors generally applied to reflect limitations of the data used. Generally used in EPA's noncancer health assessments. Acronym: Chronic RfD
	Chronic Study	Definition: A toxicity study designed to measure the (toxic) effects of chronic exposure to a chemical.
	Chronic Toxicity	Definition: The capacity of a substance to cause adverse human health effects as a result of chronic exposure.
	Co-carcinogen	Definition: An agent that, when administered with a carcinogen, enhances the activity of the carcinogen.
	Cohort Study	Definition: An epidemiologic study comparing those with an exposure of interest to those without the exposure. These two cohorts are then followed over time to determine the differences in the rates of disease between the exposure subjects.
	Confounder	Definition: A condition or variable that is both a risk factor for disease and associated with an exposure of interest. This association between the exposure of interest and the confounder (a true risk factor for disease) may make it falsely appear that the exposure of interest is associated with disease.
	Confounding Factor	Definition: See Confounder.
	Control Group	Definition: A group used as the baseline for comparison in epidemiologic studies or laboratory studies. This group is selected because it either lacks the disease of interest (case-control group) or lacks the exposure of concern (cohort study).
	Critical Concentration	Definition: An ambient chemical concentration expressed in units of µg/m³ and used in the operational derivation of the inhalation RfC. This concentration will be the NOAEL Human Equivalent Concentration (HEC) adjusted from principal study data.
	Critical Effect	Definition: The first adverse effect, or its known precursor, that occurs to the most sensitive species as the dose rate of an agent increases.
	Critical Study	Definition: The study that contributes most significantly to the qualitative and quantitative assessment of risk. Also called Principal Study.
	Developmental Toxicity	Definition: Adverse effects on the developing organism that may result from exposure prior to conception (either parent), during prenatal development, or postnatally until the time of sexual maturation. The major manifestations of developmental toxicity include death of the developing organism, structural abnormality, altered growth, and functional deficiency.
	Dose	Definition: The amount of a substance available for interactions with metabolic processes or biologically significant receptors after crossing the outer boundary of an organism. The POTENTIAL DOSE is the amount ingested, inhaled, or applied to the skin. The APPLIED DOSE is the amount presented to an absorption barrier and available for absorption (although not necessarily having yet crossed the outer boundary of the organism). The ABSORBED DOSE is the amount crossing a specific absorption barrier (e.g. the exchange boundaries of the skin, lung, and digestive tract) through uptake processes. INTERNAL DOSE is a more general term denoting the amount absorbed without respect to specific absorption barriers or exchange boundaries. The amount of the chemical available for interaction by any particular organ or cell is termed the DELIVERED or BIOLOGICALLY EFFECTIVE DOSE for that organ or cell.
	Dose-Response Assessment	Definition: A determination of the relationship between the magnitude of an administered, applied, or internal dose and a specific biological response. Response can be expressed as measured or observed incidence or change in level of response, percent response in groups of subjects (or populations), or the probability of occurrence or change in level of response within a population.
	Dose-Response Relationship	Definition: The relationship between a quantified exposure (dose) and the proportion of subjects demonstrating specific biologically significant changes in incidence and/or in degree of change (response).
	Effective Dose	Definition: The dose corresponding to a 10% increase in an adverse effect, relative to the control response. Acronym: ED₁₀
	Endpoint	Definition: An observable or measurable biological event or chemical concentration (e.g., metabolite concentration in a target tissue) used as an index of an effect of a chemical exposure.
	Epidemiology	Definition: The study of the distribution and determinants of health-related states or events in specified populations.
	Estimated Exposure Dose	Definition: The measured or calculated dose to which humans are likely to be exposed considering all sources and routes of exposure. Acronym: EED
	Excess Lifetime Risk	Definition: The additional or extra risk of developing cancer due to exposure to a toxic substance incurred over the lifetime of an individual.
	Exposure	Definition: Contact made between a chemical, physical, or biological agent and the outer boundary of an organism. Exposure is quantified as the amount of an agent available at the exchange boundaries of the organism (e.g., skin, lungs, gut).
	Exposure Assessment	Definition: An identification and evaluation of the human population exposed to a toxic agent, describing its composition and size, as well as the type, magnitude, frequency, route and duration of exposure.
	Extra Risk	Definition: A calculation of risk of adverse effects which adjusts for background incidence rates of the same effects, by estimating risk at dose d only among the fraction of the population not expected to respond to the secondary (background) causes: ER = [P(d)-P(0)/1-P(0)]. For example, if the background rate (P(0)) = 0.8 and the response rate at dose d, P(d) = .9, then ER = (0.9 - 0.8)/(1-0.8) = 0.1/0.2 = 0.5. That is, at dose d, an additional 10% of the population is expected to respond adversely. But since only 20% of the population was expected to be free of adverse effects without the exposure of interest, this 10% represents 50% of the population that would otherwise have been unharmed by this exposure. Acronym: ER
	Extrapolation, low dose	Definition: An estimate of the response at a point below the range of the experimental data, generally through the use of a mathematical model.
	Forced Expiratory Volume	Definition: The volume of air that can be forcibly exhaled during the first second of expiration following a maximal inspiration. Acronym: FEV₁
	Forced Vital Capacity	Definition: The maximal volume of air that can be exhaled as forcibly and rapidly as possible after a maximal inspiration. Acronym: FVC
	Frank Effect Level	Definition: A level of exposure or dose that produces irreversible, adverse effects at a statistically or biologically significant increase in frequency or severity between those exposed and those not exposed. Acronym: FEL
	Functional Residual Capacity	Definition: The lung volume at the end of tidal expiration (TLC - IC). Acronym: FRC
	Gamma (Multi-Hit) Model	Definition: A generalization of the one-hit model (see definition) for low-dose extrapolation.
	Guidelines (human health risk assessment)	Definition: Official, peer-reviewed documentation stating current U.S. EPA methodology in assessing risk of harm from environmental pollutants to populations. Examples: Guidelines for Carcinogenic Risk Assessment: U.S. EPA guidelines intended to guide Agency evaluation of suspect carcinogens. 66 FR 17765-17817, April 7, 2005; Guidelines for Exposure Assessment: U.S. EPA guidelines intended to guide Agency analysis of potential exposure to chemical substances. 51 FR 22888-22938, May 29,1992; Guidelines for Developmental Toxicity Risk Assessment: U.S. EPA guidelines intended to guide Agency analysis of developmental toxicity data. 51 FR 34028-34040, October 1996; Guidelines for Mutagenicity Risk Assessment: U. S. EPA guidelines intended to guide Agency analysis of mutagenicity data. 51 FR 34006-34016, September, 1986.
	Hazard	Definition: A potential source of harm.
	Hazard Assessment	Definition: The process of determining whether exposure to an agent can cause an increase in the incidence of a particular adverse health effect (e.g., cancer, birth defect) and whether the adverse health effect is likely to occur in humans.
	Hazard Characterization	Definition: A description of the potential adverse health effects attributable to a specific environmental agent, the mechanisms by which agents exert their toxic effects, and the associated dose, route, duration, and timing of exposure.
	Human Equivalent Concentration	Definition: The human concentration (for inhalation exposure) or dose (for other routes of exposure) of an agent that is believed to induce the same magnitude of toxic effect as the experimental animal species concentration or dose. This adjustment may incorporate toxicokinetic information on the particular agent, if available, or use a default procedure, such as assuming that daily oral doses experienced for a lifetime are proportional to body weight raised to the 0.75 power. Acronym: HEC
	Human Equivalent Dose	Definition: The human concentration (for inhalation exposure) or dose (for other routes of exposure) of an agent that is believed to induce the same magnitude of toxic effect as the experimental animal species concentration or dose. This adjustment may incorporate toxicokinetic information on the particular agent, if available, or use a default procedure, such as assuming that daily oral doses experienced for a lifetime are proportional to body weight raised to the 0.75 power. Acronym: HED
	Incidence	Definition: The number of new cases of a disease that develop within a specified population over a specified period of time.
	Incidence Rate	Definition: The ratio of new cases within a population to the total population at risk given a specified period of time.
	Individual Risk	Definition: The probability that an individual will experience an adverse effect.
	Inhalation Unit Risk	Definition: The upper-bound excess lifetime cancer risk estimated to result from continuous exposure to an agent at a concentration of 1 µg/m³ in air. The interpretation of inhalation unit risk would be as follows: if unit risk = 2 × 10⁻⁶ per µg/m³, 2 excess cancer cases (upper bound estimate) are expected to develop per 1,000,000 people if exposed daily for a lifetime to 1 µg of the chemical per m³ of air.
	Initiation	Definition: The first stage of carcinogenesis.
	Interspecies Dose Conversion	Definition: The process of extrapolating from animal doses to human equivalent doses.
	Latency Period	Definition: The time between first exposure to an agent and manifestation or detection of a health effect of interest.
	Limited Evidence	Definition: A term used in evaluating study data for the classification of a carcinogen by the 1986 U.S. EPA guidelines for carcinogen risk assessment. This classification indicates that a causal interpretation is credible but that alternative explanations such as chance, bias, and confounding variables could not be completely excluded.
	Linear Dose Response	Definition: A pattern of frequency or severity of biological response that varies directly with the amount of dose of an agent.
	Linearized Multistage Procedure	Definition: A modification of the multistage model, used for estimating carcinogenic risk, that incorporates a linear upper bound on extra risk for exposures below the experimental range.
	Logistic Model	Definition: A dose-response model used for low-dose extrapolation.
	Longer-Term Exposure	Definition: Repeated exposure by the oral, dermal, or inhalation route for more than 30 days, up to approximately 10% of the life span in humans (more than 30 days up to approximately 90 days in typically used laboratory animal species).
	Lower Limit on Effective Dose ₁₀	Definition: The 95% lower confidence limit of the dose of a chemical needed to produce an adverse effect in 10 percent of those exposed to the chemical, relative to control. Acronym: LED₁₀
	Lowest-Observed-Adverse-Effect Level	Definition: The lowest exposure level at which there are biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control group. Acronym: LOAEL
	Lowest-Observed-Effect Level	Definition: In a study, the lowest dose or exposure level at which a statistically or biologically significant effect is observed in the exposed population compared with an appropriate unexposed control group. Acronym: LEL, LOEL
	Malignant Tumor	Definition: An abnormal growth of tissue which can invade adjacent or distant tissues.
	Margin of Exposure	Definition: The LED₁₀ or other point of departure divided by the actual or projected environmental exposure of interest. Acronym: MOE
	Mass Median Aerodynamic Diameter	Definition: Median of the distribution of airborne particle mass with respect to the aerodynamic diameter. MMADs are usually accompanied by the geometric standard deviation (g or sigma g) which characterizes the variability of the particle size distribution. Acronym: MMAD
	Maximum Likelihood Estimate	Definition: Statistical method for estimating a population parameter most likely to have produced the sample observations. Acronym: MLE
	Maximum Likelihood Method	Definition: Statistical method for estimating a population parameter most likely to have produced the sample observations. Acronym: ML Method
	Metastasis	Definition: The dissemination or secondary growth of a malignant tumor at a site distant from the primary tumor.
	Model	Definition: A mathematical function with parameters that can be adjusted so the function closely describes a set of empirical data. A mechanistic model usually reflects observed or hypothesized biological or physical mechanisms, and has model parameters with real world interpretation. In contrast, statistical or empirical models selected for particular numerical properties are fitted to data; model parameters may or may not have real world interpretation. When data quality is otherwise equivalent, extrapolation from mechanistic models (e.g., biologically based dose-response models) often carries higher confidence than extrapolation using empirical models (e.g., logistic model).
	Modifying Factor	Definition: A factor used in the derivation of a reference dose or reference concentration. The magnitude of the MF reflects the scientific uncertainties of the study and database not explicitly treated with standard uncertainty factors (e.g., the completeness of the overall database). A MF is greater than zero and less than or equal to 10, and the default value for the MF is 1. [Use of a modifying factor was discontinued in 2004.] Acronym: MF
	Monte Carlo Technique	Definition: A repeated random sampling from the distribution of values for each of the parameters in a calculation (e.g., lifetime average daily exposure), to derive a distribution of estimates (of exposures) in the population.
	Multistage Model	Definition: A mathematical function used to extrapolate the probability of cancer from animal bioassay data.
	Multistage Weibull Model	Definition: A dose-response model for low-dose extrapolation that includes a term for decreased survival time associated with tumor incidence.
	Mutagen	Definition: A substance that can induce an alteration in the structure of DNA.
	Neoplasm	Definition: An abnormal growth of tissue that may be benign or malignant.
	No-Observed-Adverse-Effect Level	Definition: The highest exposure level at which there are no biologically significant increases in the frequency or severity of adverse effect between the exposed population and its appropriate control; some effects may be produced at this level, but they are not considered adverse or precursors of adverse effects. Acronym: NOAEL
	No-Observed-Effect Level	Definition: An exposure level at which there are no statistically or biologically significant increases in the frequency or severity of any effect between the exposed population and its appropriate control. Acronym: NOEL
	Non-Linear Dose Response	Definition: A pattern of frequency or severity of biological response that does not vary directly with the amount of dose of an agent.
	Odds Ratio	Definition: A relative measure of the difference in exposure between the diseased (cases) and not diseased (controls) individuals in a case-control study. The OR is interpreted similarly to the relative risk. Acronym: OR
	Oncogenic	Definition: Resulting from a gene that can induce neoplastic transformations in the cell in which it occurs or into which it is introduced.
	One Hit Model	Definition: A dose-response model based on a mechanistic argument that there is a response after a target site has been hit by a single biologically effective unit of dose within a given time period.
	Oral Slope Factor	Definition: An upper bound, approximating a 95% confidence limit, on the increased cancer risk from a lifetime oral exposure to an agent. This estimate, usually expressed in units of proportion (of a population) affected per mg/kg-day, is generally reserved for use in the low-dose region of the dose-response relationship, that is, for exposures corresponding to risks less than 1 in 100.
	Organoleptic	Definition: Affecting or involving a sense organ such as that of taste, smell, or sight.
	Pharmacodynamics	Definition: See Toxicodynamics.
	Pharmacokinetics	Definition: See Toxicokinetics.
	Physiologically Based Pharmacokinetic Model	Definition: A model that estimates the dose to a target tissue or organ by taking into account the rate of absorption into the body, distribution among target organs and tissues, metabolism, and excretion. Acronym: PBPK Model
	Point of Departure	Definition: The dose-response point that marks the beginning of a low-dose extrapolation. This point can be the lower bound on dose for an estimated incidence or a change in response level from a dose-response model (BMD), or a NOAEL or LOAEL for an observed incidence, or change in level of response.
	ppb	Definition: A unit of measure expressed as parts per billion. Equivalent to 1 x 10⁻⁹.
	ppm	Definition: A unit of measure expressed as parts per million. Equivalent to 1 x 10⁻⁶.
	Prevalence	Definition: The proportion of disease cases that exist within a population at a specific point in time, relative to the number of individuals within that population at the same point in time.
	Principal Study	Definition: See Critical Study.
	Probit Model	Definition: A dose-response model.
	Promoter	Definition: An agent that is not carcinogenic itself, but when administered after an initiator of carcinogenesis, stimulates the clonal expansion of the initiated cell to produce a neoplasm.
	Proportionate Mortality Ratio	Definition: The proportion of deaths due to the disease of interest in the exposed population divided by the proportion of deaths due to the disease of interest in the unexposed or reference population. It is frequently converted to a percent by multiplying the ratio by 100. Acronym: PMR
	Prospective Study	Definition: See Cohort Study.
	Reference Concentration	Definition: An estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark concentration, with uncertainty factors generally applied to reflect limitations of the data used. Generally used in EPA's noncancer health assessments. [Durations include acute, short-term, subchronic, and chronic and are defined individually in this glossary]. Acronym: RfC
	Reference Dose	Definition: An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark dose, with uncertainty factors generally applied to reflect limitations of the data used. Generally used in EPA's noncancer health assessments. [Durations include acute, short-term, subchronic, and chronic and are defined individually in this glossary]. Acronym: RfD
	Reference Group	Definition: See Control Group.
	Reference Value	Definition: An estimate of an exposure for a given duration to the human population (including susceptible subgroups) that is likely to be without an appreciable risk of adverse health effects over a lifetime. It is derived from a BMDL, a NOAEL, a LOAEL, or another suitable point of departure, with uncertainty/variability factors applied to reflect limitations of the data used. [Durations include acute, short-term, subchronic, and chronic and are defined individually in this glossary.] [Reference value is a term proposed in the report, "A Review of the Reference Dose and Reference Concentration Processes" (EPA, 2002), and is a generic term not specific to a given route of exposure. EPA develops numerical toxicity values for the RfD and RfC only; no numerical toxicity values are developed for the RfV.] Acronym: RfV
	Regional Deposited Dose	Definition: The deposited dose of particles calculated for a respiratory tract region of interest (r) as related to an observed toxicity. For respiratory effects of particles, the deposited dose is adjusted for ventilatory volumes and the surface area of the respiratory region effected (mg/min-sq. cm). For extra respiratory effects of particles, the deposited dose in the total respiratory system is adjusted for ventilatory volumes and body weight (mg/min-kg). Acronym: RDD
	Regional Deposited Dose Ratio	Definition: The ratio of the regional deposited dose calculated for a given exposure in the animal species of interest to the regional deposited dose of the same exposure in a human. This ratio is used to adjust the exposure effect level for interspecies dosimetric differences to derive a human equivalent concentration for particles. Acronym: RDDR
	Regional Gas Dose	Definition: The gas dose calculated for the region of interest as related to the observed effect for respiratory effects. The deposited dose is adjusted for ventilatory volumes and the surface area of the respiratory region effected (mg/min-sq.cm).
	Regional Gas Dose Ratio	Definition: The ratio of the regional gas dose calculated for a given exposure in the animal species of interest to the regional gas dose of the same exposure in humans. This ratio is used to adjust the exposure effect level for interspecies dosimetric differences to derive a human equivalent concentration for gases with respiratory effects. Acronym: RGDR
	Relative Risk	Definition: The relative measure of the difference in risk between the exposed and unexposed populations in a cohort study. The relative risk is defined as the rate of disease among the exposed divided by the rate of the disease among the unexposed. A relative risk of 2 means that the exposed group has twice the disease risk as the unexposed group. Acronym: RR
	Reserve Volume	Definition: The volume of air remaining in the lungs after a maximal expiration.
	Residual Volume	Definition: The lung volume after maximal expiration (TLC - VC). Acronym: RV
	Risk Assessment (human health)	Definition: The evaluation of scientific information on the hazardous properties of environmental agents (hazard characterization), the dose-response relationship (dose-response assessment), and the extent of human exposure to those agents (exposure assessment). The product of the risk assessment is a statement regarding the probability that populations or individuals so exposed will be harmed and to what degree (risk characterization).
	Risk Characterization	Definition: The integration of information on hazard, exposure, and dose-response to provide an estimate of the likelihood that any of the identified adverse effects will occur in exposed people.
	Risk Difference	Definition: See Additional Risk.
	Risk (human health)	Definition: The probability of adverse effects resulting from exposure to an environmental agent or mixture of agents.
	Risk Management (human health)	Definition: A decision making process that accounts for political, social, economic and engineering implications together with risk-related information in order to develop, analyze and compare management options and select the appropriate managerial response to a potential chronic health hazard.
	Risk Ratio	Definition: See Relative Risk. Acronym: RR
	Short Term Exposure	Definition: Repeated exposure by the oral, dermal, or inhalation route for more than 24 hours, up to 30 days.
	Short Term Reference Concentration	Definition: An estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure for short-term duration (up to 30 days) to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark concentration, with uncertainty factors generally applied to reflect limitations of the data used. Generally used in EPA's noncancer health assessments. Acronym: Short Term RfC
	Short Term Reference Dose	Definition: An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure for a short-term duration (up to 30 days) to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark dose, with uncertainty factors generally applied to reflect limitations of the data used. Generally used in EPA's noncancer health assessments. Acronym: Short Term RfD
	Sigma g	Definition: Geometric standard deviation. (See Mass Median Aerodynamic Diameter.) Acronym: s g
	Slope Factor	Definition: An upper bound, approximating a 95% confidence limit, on the increased cancer risk from a lifetime exposure to an agent. This estimate, usually expressed in units of proportion (of a population) affected per mg/kg-day, is generally reserved for use in the low-dose region of the dose-response relationship, that is, for exposures corresponding to risks less than 1 in 100.
	Standardized Mortality Ratio	Definition: This is the relative measure of the difference in risk between the exposed and unexposed populations in a cohort study. The SMR is similar to the relative risk in both definition and interpretation. This measure is usually standardized to control for any differences in age, sex, and/or race between the exposed and reference populations. It is frequently converted to a percent by multiplying the ratio by 100. Acronym: SMR
	Statistical Significance	Definition: The probability that a result is not likely to be due to chance alone. By convention, a difference between two groups is usually considered statistically significant if chance could explain it only 5% of the time or less. Study design considerations may influence the a priori choice of a different level of statistical significance.
	Subchronic Exposure	Definition: Repeated exposure by the oral, dermal, or inhalation route for more than 30 days, up to approximately 10% of the life span in humans (more than 30 days up to approximately 90 days in typically used laboratory animal species). [See also longer-term exposure.]
	Subchronic Reference Concentration	Definition: An estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure for a subchronic duration (up to 10% of average lifespan) to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark concentration, with uncertainty factors generally applied to reflect limitations of the data used. Generally used in EPA's noncancer health assessments. Acronym: Subchronic RfC
	Subchronic Reference Dose	Definition: An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure for a subchronic duration (up to 10% of average lifespan) to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark dose, with uncertainty factors generally applied to reflect limitations of the data used. Generally used in EPA's noncancer health assessments. Acronym: Subchronic RfD
	Subchronic Study	Definition: A toxicity study designed to measure effects from subchronic exposure to a chemical.
	Sufficient Evidence	Definition: A term used in evaluating study data for the classification of a carcinogen under the 1986 U.S. EPA guidelines for carcinogen risk assessment. This classification indicates that there is a causal relationship between the agent or agents and human cancer.
	Superfund	Definition: Federal authority, established by the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) in 1980, to respond directly to releases or threatened releases of hazardous substances that may endanger health or welfare.
	Supporting Studies	Definition: Studies that contain information useful for providing insight and support for conclusions.
	Susceptibility	Definition: Increased likelihood of an adverse effect, often discussed in terms of relationship to a factor that can be used to describe a human subpopulation (e.g., life stage, demographic feature, or genetic characteristic).
	Susceptible Subgroups	Definition: May refer to life stages, for example, children or the elderly, or to other segments of the population, for example, asthmatics or the immune-compromised, but are likely to be somewhat chemical-specific and may not be consistently defined in all cases.
	Systemic Effects	Definition: Toxic effects as a result of absorption and distribution of a toxicant to a site distant from its entry point.
	Systemic Toxicity	Definition: Toxic effects as a result of absorption and distribution of a toxicant to a site distant from its entry point.
	Target Organ	Definition: The biological organ(s) most adversely affected by exposure to a chemical, physical, or biological agent.
	Teratogenic	Definition: Structural developmental defects due to exposure to a chemical agent during formation of individual organs.
	Threshold	Definition: The dose or exposure below which no deleterious effect is expected to occur.
	Threshold Limit Value	Definition: Recommended guidelines for occupational exposure to airborne contaminants published by the American Conference of Governmental Industrial Hygienists (ACGIH). TLVs represent the average concentration in mg/m³ for an 8-hour workday and a 40-hour work week to which nearly all workers may be repeatedly exposed, day after day, without adverse effect. Acronym: TLV
	Tidal Volume	Definition: The volume of air inhaled/exhaled during normal breathing. Acronym: VT
	Total Lung Volume	Definition: The lung volume at maximal inspiration. Acronym: TLV
	Toxic Substance	Definition: A chemical, physical, or biological agent that may cause an adverse effect or effects to biological systems.
	Toxicity	Definition: Deleterious or adverse biological effects elicited by a chemical, physical, or biological agent.
	Toxicodynamics	Definition: The determination and quantification of the sequence of events at the cellular and molecular levels leading to a toxic response to an environmental agent (sometimes referred to as pharmacodynamics).
	Toxicokinetics	Definition: The determination and quantification of the time course of absorption, distribution, biotransformation, and excretion of chemicals (sometimes referred to as pharmacokinetics).
	Toxicology	Definition: The study of harmful interactions between chemical, physical, or biological agents and biological systems.
	Tumor	Definition: An abnormal, uncontrolled growth of cells. Synonym: neoplasm
	Tumor Progression	Definition: Under the Armitage-Doll multistage theory of cancer development, the transition of a cell line between the stages which lead to cancer.
	Uncertainty	Definition: Uncertainty occurs because of a lack of knowledge. It is not the same as variability. For example, a risk assessor may be very certain that different people drink different amounts of water but may be uncertain about how much variability there is in water intakes within the population. Uncertainty can often be reduced by collecting more and better data, whereas variability is an inherent property of the population being evaluated. Variability can be better characterized with more data but it cannot be reduced or eliminated. Efforts to clearly distinguish between variability and uncertainty are important for both risk assessment and risk characterization.
	Uncertainty Factor	Definition: One of several, generally 10-fold, default factors used in operationally deriving the RfD and RfC from experimental data. The factors are intended to account for (1) variation in susceptibility among the members of the human population (i.e., inter-individual or intraspecies variability); (2) uncertainty in extrapolating animal data to humans (i.e., interspecies uncertainty); (3) uncertainty in extrapolating from data obtained in a study with less-than-lifetime exposure (i.e., extrapolating from subchronic to chronic exposure); (4) uncertainty in extrapolating from a LOAEL rather than from a NOAEL; and (5) uncertainty associated with extrapolation when the database is incomplete. Acronym: UF
	Unit Risk	Definition: The upper-bound excess lifetime cancer risk estimated to result from continuous exposure to an agent at a concentration of 1 µg/L in water, or 1 µg/m³ in air. The interpretation of unit risk would be as follows: if unit risk = 2 × 10⁻⁶ per µg/L, 2 excess cancer cases (upper bound estimate) are expected to develop per 1,000,000 people if exposed daily for a lifetime to 1 µg of the chemical per liter of drinking water.
	Upper Bound	Definition: A plausible upper limit to the true value of a quantity. This is usually not a true statistical confidence limit.
	Variability	Definition: Variability refers to true heterogeneity or diversity. For example, among a population that drinks water from the same source and with the same contaminant concentration, the risks from consuming the water may vary. This may be due to differences in exposure (i.e., different people drinking different amounts of water and having different body weights, different exposure frequencies, and different exposure durations) as well as differences in response (e.g., genetic differences in resistance to a chemical dose). Those inherent differences are referred to as variability. Differences among individuals in a population are referred to as inter-individual variability, differences for one individual over time is referred to as intra-individual variability.
	Variability Factor	Definition: One of several, generally 10-fold, default factors used in operationally deriving the RfD and RfC from experimental data. The factors are intended to account for (1) variation in susceptibility among the members of the human population (i.e., inter-individual or intraspecies variability); (2) uncertainty in extrapolating animal data to humans (i.e., interspecies uncertainty); (3) uncertainty in extrapolating from data obtained in a study with less-than-lifetime exposure (i.e., extrapolating from subchronic to chronic exposure); (4) uncertainty in extrapolating from a LOAEL rather than from a NOAEL; and (5) uncertainty associated with extrapolation when the database is incomplete.
	Vital Capacity	Definition: The maximum volume that can be exhaled in a single breath (TLC-RC). Acronym: VC
	Weibull Model	Definition: A dose-response model.
	Weight-of-Evidence for Carcinogenicity	Definition: A system used by the U.S. EPA for characterizing the extent to which the available data support the hypothesis that an agent causes cancer in humans. Under EPA's 1986 risk assessment guidelines, the WOE was described by categories "A through E", Group A for known human carcinogens through Group E for agents with evidence of noncarcinogenicity. The approach outlined in EPA's guidelines for carcinogen risk assessment (2005) considers all scientific information in determining whether and under what conditions an agent may cause cancer in humans, and provides a narrative approach to characterize carcinogenicity rather than categories. Five standard weight-of-evidence descriptors are used as part of the narrative. Acronym: WOE for Carcinogenicity

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