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### IRIS Glossary/Acronyms & Abbreviations This glossary contains definitions of terms used frequently in IRIS. It is intended to assist users in understanding terms that appear in U.S. EPA hazard and doseresponse assessments. These definitions are not all -encompassing, but are useful "working definitions". It is assumed that the user has some familiarity with risk assessment and health science. For terms that are n ot included in this glossary, the user should refer to standard health science, biost atistics and medical textbooks and dictionaries. [link to IRIS Archive Glossary]

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z 

### A Acceptable Daily Intake (ADI) : 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. Acute Exposure: Exposure by the oral, dermal, or inhalation route for 24 hours or less. Acute Reference Concentration (RfC): An estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inha lation 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 li mitations of the data used. Generally used in EPA's noncancer health assessment s.



## Integrated Risk Information System (IRIS) Page 1 of 18 Site Help & Tools

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12/6/2011 http://www.epa.gov/NCEA/iris/help_gloss.htmAcute Reference Dose (RfD): 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 subgro ups) 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 use d in EPA's noncancer health assessments. Acute Toxicity: Any poisonous effect produced within a short period of time following an exposure, usually 24 to 96 hours. Additional Risk (Added, Attributable Risk or Risk D ifference) (AR): The calculated difference in risk of a particular condi tion between those who are exposed and those who are not. This measure is deri ved by subtracting the rate (usually incidence or mortality) of the disease amo ng 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 e xposure. Adverse Effect: A biochemical change, functional impairment, or pat hologic lesion that affects the performance of the whole organism, or reduces an organism's ability to respond to an additional environmental c hallenge. Aerodynamic Diameter: The diameter of a sphere with unit density that ha s aerodynamic behavior identical to that of the parti cle in question; an expression of aerodynamic behavior of an irregularly shaped parti cle in terms of the diameter of an idealized particle. Particles having the same ae rodynamic diameter may have different dimensions and shapes. Aerosol: A suspension of liquid or solid particles in air. Anecdotal Data: Data based on the description of individual cases rather than controlled studies. Average Daily Dose (ADD): Dose rate averaged over a pathway-specific period of exposure expressed as a daily dose on a per-unit-bo dy-weight basis. The ADD is usually expressed in terms of mg/kg-day or other ma ss-time units. 

### B Background Levels: Two types of background levels may exist for chemic al substances: (a) Naturally occurring levels: Ambientconcentrations of substances present in the environment, without human influence ; (b) Anthropogenic levels: Concentrations of substances present in the environ ment due to human-made, nonsite sources (e.g., automobiles, industries). Benchmark Dose (BMD) or Concentration (BMC): 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. BMDL or BMCL: A statistical lower confidence limit on the dose o r concentration at the BMD or BMC, respectively. 

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12/6/2011 http://www.epa.gov/NCEA/iris/help_gloss.htmBenchmark Response (BMR): An adverse effect, used to define a benchmark

dose from which an RfD (or RfC) can be developed. T he 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 anim al experiments. Benign Tumor : A tumor that does not spread to a secondary local ization, but may impair normal biological function through obstructi on or may progress to malignancy later. Bioassay: An assay for determining the potency (or concentra tion) of a substance that causes a biological change in experimental ani mals. Bioavailability: The degree to which a substance becomes available t o the target tissue after administration or exposure. Biologically Based Dose Response (BBDR) model: A predictive model that describes biological processes at the cellular and molecular level linking the target organ dose to the adverse effect. Blood-to-air Partition Coefficient: A ratio of a chemical's concentration between blood and air when at equilibrium. 

### C CAS Registry Number: The Chemical Abstract Service Registry Number (CAS RN) is an unique numeric identifier, designed to design ate only one substance so it can be referenced by many Government Agencies and/or in ternationally. Cancer: A disease of heritable, somatic mutations affectin g cell growth and differentiation, characterized by an abnormal, unco ntrolled growth of cells. Carcinogen: An agent capable of inducing cancer. Carcinogenesis: 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 po pulation of altered cells. Case-control Study: An epidemiologic study contrasting those with the d isease of interest (cases) to those without the disease (cont rols). The groups are then compared with respect to exposure history, to ascertain whether they differ in the proportion exposed to the chemical(s) under investi gation. Chronic Effect: An effect that occurs as a result of repeated or l ong term (chronic) exposures. Chronic Exposure: Repeated exposure by the oral, dermal, or inhalati on route for more than approximately 10% of the life span in hum ans (more than approximately 90 days to 2 years in typically used laboratory ani mal species). Chronic Reference Concentration (RfC): An estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inha lation exposure for a chronic duration (up to a lifetime) to the human population (including sensitive subgroups) 

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12/6/2011 http://www.epa.gov/NCEA/iris/help_gloss.htmthat 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 li mitations of the data used. Generally used in EPA's noncancer health assessment s. Chronic Reference Dose (RfD): 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 sensit ive 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 uncert ainty factors generally applied to reflect limitations of the data used. Ge nerally used in EPA's noncancer health assessments. Chronic Study: A toxicity study designed to measure the (toxic) e ffects of chronic exposure to a chemical. Chronic Toxicity: The capacity of a substance to cause adverse human health effects as a result of chronic exposure. Co-carcinogen: An agent that, when administered with a carcinogen, enhances the activity of the carcinogen. Cohort Study (or Prospective Study): An epidemiologic study comparing those with an exposure of interest to those without the e xposure. These two cohorts are then followed over time to determine the difference s in the rates of disease between the exposure subjects. Confounder (or Confounding Factor): 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 int erest is associated with disease. Control Group (or Reference Group): A group used as the baseline for comparison in epidemiologic studies or laboratory s tudies. This group is selected because it either lacks the disease of interest (ca se-control group) or lacks the exposure of concern (cohort study). Critical Concentration: An ambient chemical concentration expressed in uni ts of μg/m 3 and used in the operational derivation of the inha lation RfC. This concentration will be the NOAEL Human Equivalent Co ncentration (HEC) adjusted from principal study data. Critical Effect: The first adverse effect, or its known precursor, t hat occurs to the most sensitive species as the dose rate of an agentincreases. Critical Study: The study that contributes most significantly to t he qualitative and quantitative assessment of risk. Also called Princi pal Study. 

### D Developmental Toxicity: Adverse effects on the developing organism that may result from exposure prior to conception (either pa rent), during prenatal 

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12/6/2011 http://www.epa.gov/NCEA/iris/help_gloss.htmdevelopment, or postnatally until the time of sexua l maturation. The major

manifestations of developmental toxicity include de ath of the developing organism, structural abnormality, altered growth, and functio nal deficiency.
Dose: The amount of a substance available for interactio ns with metabolic processes or biologically significant receptors aft er crossing the outer boundary of an organism. The POTENTIAL DOSE is the amount inges ted, 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 theamount 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 abs orption barriers or exchange boundaries. The amount of the chemical available fo r interaction by any particular organ or cell is termed the DELIVERED or BIOLOGICAL LY EFFECTIVE DOSE for that organ or cell. Dose-Response Assessment: 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 res ponse within a population. Dose-Response Relationship: 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 (re sponse). 

### E Effective Dose (ED 10 ): The dose corresponding to a 10% increase in an adv erse effect, relative to the control response. Endpoint: An observable or measurable biological event or ch emical concentration (e.g., metabolite concentration in a target tissue) used as an index of an effect of a chemical exposure. Epidemiology: The study of the distribution and determinants of health-related states or events in specified populations. Estimated Exposure Dose (EED): The measured or calculated dose to which humans are likely to be exposed considering all sou rces and routes of exposure. Excess Lifetime Risk: The additional or extra risk of developing cancer due to exposure to a toxic substance incurred over the lifetime of an individual. Exposure: Contact made between a chemical, physical, or biol ogical agent and the outer boundary of an organism. Exposure is quantifi ed as the amount of an agent available at the exchange boundaries of the organis m (e.g., skin, lungs, gut). Exposure Assessment: An identification and evaluation of the human popu lation exposed to a toxic agent, describing its compositio n and size, as well as the type, magnitude, frequency, route and duration of exposure. 

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12/6/2011 http://www.epa.gov/NCEA/iris/help_gloss.htmExtra Risk (ER): A calculation of risk of adverse effects which adj usts for

background incidence rates of the same effects, by estimating risk at dose d only among the fraction of the population not expected t o respond to the secondary (background) causes: ER = [P(d)-P(0)/1-P(0)]. For e xample, 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 additi onal 10% of the population is expected to respond adversely. But since only 20% o f 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 bee n unharmed by this exposure. Extrapolation, low dose: An estimate of the response at a point below the r ange of the experimental data, generally through the use of a mathematical model. 

### F Forced Expiratory Volume (FEV 1 ): The volume of air that can be forcibly exhaled during the first second of expiration following a m aximal inspiration. Forced Vital Capacity (FVC): The maximal volume of air that can be exhaled as forcibly and rapidly as possible after a maximal in spiration. Frank Effect Level (FEL): A level of exposure or dose that produces irreversi ble, adverse effects at a statistically or biologically significant increase in frequency or severity between those exposed and those not expose d. Functional Residual Capacity (FRC): The lung volume at the end of tidal expiration (TLC - IC). 

### G Gamma (Multi-hit) Model: A generalization of the one-hit model (see definit ion) for low-dose extrapolation. The probability P(d) th at an individual will respond to lifetime, continuous exposure to dose d is given by

Guidelines (human health risk assessment): 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. E PA guidelines intended to guide Agency evaluation of suspect carc inogens. 66 FR 17765-17817, April 7, 2005. 

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12/6/2011 http://www.epa.gov/NCEA/iris/help_gloss.htmGuidelines for Exposure Assessment: U.S. EPA guidel ines intended to

guide Agency analysis of potential exposure to chem ical substances. 51 FR 22888-22938, May 29,1992. Guidelines for Developmental Toxicity Risk Assessme nt: U.S. EPA guidelines intended to guide Agency analysis of dev elopmental toxicity data. 51 FR 34028-34040, October 1996. Guidelines for Mutagenicity Risk Assessment: U. S. EPA guidelines intended to guide Agency analysis of mutagenicity d ata. 51 FR 34006- 34016, September, 1986. 

### H Hazard: A potential source of harm. Hazard Assessment: The process of determining whether exposure to an a gent can cause an increase in the incidence of a particu lar adverse health effect (e.g., cancer, birth defect) and whether the adverse healt h effect is likely to occur in humans. Hazard Characterization: A description of the potential adverse health effe cts 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 (HEC) or Dose (HED): The human concentration (for inhalation exposure) or dose (fo r other routes of exposure) of an agent that is believed to induce the same magnitudeof toxic effect as the experimental animal species concentration or dose. This adjustment may incorporate toxicokinetic information on the partic ular 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 . 

### I Incidence: The number of new cases of a disease that develop within a specified population over a specified period of time. Incidence Rate: The ratio of new cases within a population to the total population at risk given a specified period of time. Individual Risk: The probability that an individual will experience an adverse effect. Inhalation Unit Risk: The upper-bound excess lifetime cancer risk estima ted to result from continuous exposure to an agent at a co ncentration of 1 μg/m 3 in air. The interpretation of inhalation unit risk would beas follows: if unit risk = 2 × 10 -6 per μg/m 3 , 2 excess cancer cases (upper bound estimate) are expected to develop 

### Page 7 of 18 Site Help & Tools

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of air. Initiation: The first stage of carcinogenesis. Interspecies Dose Conversion: The process of extrapolating from animal doses to human equivalent doses. 

### L Latency Period: The time between first exposure to an agent and man ifestation or detection of a health effect of interest. Limited Evidence: A term used in evaluating study data for the class ification of a carcinogen by the 1986 U.S. EPA guidelines for carc inogen risk assessment. This classification indicates that a causal interpretati on is credible but that alternative explanations such as chance, bias, and confounding variables could not be completely excluded. Linear Dose Response: A pattern of frequency or severity of biological response that varies directly with the amount of dose of an agent. Linearized Multistage Procedure: 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: A dose-response model used for low-dose extrapolat ion, of the form:

Longer-Term Exposure: Repeated exposure by the oral, dermal, or inhalati on 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 t ypically used laboratory animal species). Lower Limit on Effective Dose 10 (LED 10 ): 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. Lowest-Observed-Adverse-Effect Level (LOAEL): 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. 

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12/6/2011 http://www.epa.gov/NCEA/iris/help_gloss.htmLowest-Observed-Effect Level (LOEL or LEL): In a study, the lowest dose or

exposure level at which a statistically or biologic ally significant effect is observed in the exposed population compared with an appropriateunexposed control group. 

### M Malignant Tumor: An abnormal growth of tissue which can invade adjac ent or distant tissues. Margin of Exposure (MOE): The LED 10 or other point of departure divided by the actual or projected environmental exposure of interest. Mass Median Aerodynamic Diameter (MMAD): Median of the distribution of airborne particle mass with respect to the aerodyna mic diameter. MMADs are usually accompanied by the geometric standard devia tion (g or sigma g) which characterizes the variability of the particle size distribution. Maximum Likelihood (ML) Method, Maximum Likelihood Estimate (MLE): Statistical method for estimating a population para meter most likely to have produced the sample observations. Metastasis: The dissemination or secondary growth of a malignan t tumor at a site distant from the primary tumor. Model: 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 phy sical mechanisms, and has model parameters with real world interpretation. In contr ast, statistical or empirical models selected for particular numerical properties are fitted to data; model parameters may or may not have real world interpret ation. When data quality is otherwise equivalent, extrapolation from mechanisti c models (e.g., biologically based dose-response models) often carries higher co nfidence than extrapolation using empirical models (e.g., logistic model). Modifying Factor (MF): A factor used in the derivation of a reference dose or reference concentration. The magnitude of the MF re flects the scientific uncertainties of the study and database not explici tly 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.] Monte Carlo Technique : 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 (o f exposures) in the population. 

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12/6/2011 http://www.epa.gov/NCEA/iris/help_gloss.htmMultistage Model: A mathematical function used to extrapolate the pro bability of

cancer from animal bioassay data, using the form:

Multistage Weibull Model: A dose-response model for low-dose extrapolation th at includes a term for decreased survival time associa ted with tumor incidence:

Mutagen: A substance that can induce an alteration in the st ructure of DNA. 

### N Neoplasm: An abnormal growth of tissue that may be benign or malignant. No-Observed-Adverse-Effect Level (NOAEL): The highest exposure level at which there are no biologically significant increas es in the frequency or severity of adverse effect between the exposed population and i ts appropriate control; some effects may be produced at this level, but they are not considered adverse or precursors of adverse effects. No-Observed-Effect Level (NOEL): An exposure level at which there are no statistically or biologically significant increasesin the frequency or severity of any effect between the exposed population and its appro priate control. Non-Linear Dose Response: A pattern of frequency or severity of biological response that does not vary directly with the amoun t of dose of an agent. 

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### O

Odds Ratio (OR): A relative measure of the difference in exposure b etween the diseased (cases) and not diseased (controls) indivi duals in a case-control study. The OR is interpreted similarly to the relative risk. Oncogenic: Resulting from a gene that can induce neoplastic tr ansformations in the cell in which it occurs or into which it is int roduced. One Hit Model: A dose-response model based on a mechanistic argum ent that there is a response after a target site has been hi t by a single biologically effective unit of dose within a given time period. The form of the model, a special case of the gamma, multistage, and Weibull models, is given by:

Oral Slope Factor: An upper bound, approximating a 95% confidence limi t, on the increased cancer risk from a lifetime oral exposureto an agent. This estimate, usually expressed in units of proportion (of a popu lation) affected per mg/kg- day, is generally reserved for use in the low-dose region o f the dose-response relationship, that is, for exposures corresponding to risks less than 1 in 100. Organoleptic: Affecting or involving a sense organ such as that o f taste, smell, or sight. 

### P Physiologically Based Pharmacokinetic (PBPK) Model: A model that estimates the dose to a target tissue or organ by taking intoaccount the rate of absorption into the body, distribution among target organs and tissues, metabolism, and excretion. Point of Departure: The dose-response point that marks the beginning o f a lowdose extrapolation. This point can be the lower bou nd 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 changein level of response. ppb: A unit of measure expressed as parts per billion. E quivalent to 1 x 10 -9

. ppm: A unit of measure expressed as parts per million. E quivalent to 1 x 10 -6

. Prevalence: The proportion of disease cases that exist within a population at a specific point in time, relative to the number of i ndividuals within that population at the same point in time. 

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12/6/2011 http://www.epa.gov/NCEA/iris/help_gloss.htmProbit Model: A dose-response model of the form:

Promoter: 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 (PMR): The proportion of deaths due to the disease of interest in the exposed population divid ed 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 th e ratio by 100. Prospective Study: See cohort study. 

### R Reference Concentration (RfC): An estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation e xposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It c an be derived from a NOAEL, LOAEL, or benchmark concentration, with uncertainty factor s generally applied to reflect limitations of the data used. Generally used in EPA 's noncancer health assessments. [Durations include acute, short-term, subchronic, a nd chronic and are defined individually in this glossary]. Reference Dose (RfD): An estimate (with uncertainty spanning perhaps an o rder of magnitude) of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without an apprecia ble 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 li mitations of the data used. Generally used in EPA's noncancer health assessment s. [Durations include acute, short-term, subchronic, and chronic and are defined individually in this glossary]. Reference Value (RfV): 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 l ifetime. It is derived from a BMDL, a NOAEL, a LOAEL, or another suitable point of depa rture, with uncertainty/variability factors applied to reflect limitations of the data used. [Durations include acute, short-term, subchronic, a nd chronic and are defined individually in this glossary.] [Reference value isa term proposed in the report, "A Review of the Reference Dose and Reference Concentr ation Processes" (EPA, 2002), and is a generic term not specific to a given route of exposure. EPA develops 

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12/6/2011 http://www.epa.gov/NCEA/iris/help_gloss.htmnumerical toxicity values for the RfD and RfC only; no numerical toxicity values are

developed for the RfV.] Regional Deposited Dose (RDD): 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 dos e is adjusted for ventilatory volumes and the surface area of the respiratory reg ion effected (mg/min-sq. cm). For extra respiratory effects of particles, the dep osited dose in the total respiratory system is adjusted for ventilatory volumes and bodyweight (mg/min-kg). Regional Deposited Dose Ratio (RDDR): 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. Thi s ratio is used to adjust the exposure effect level for interspecies dosimetric d ifferences to derive a human equivalent concentration for particles. Regional Gas Dose: The gas dose calculated for the region of interest as related to the observed effect for respiratory effects. The de posited dose is adjusted for ventilatory volumes and the surface area of the res piratory region effected (mg/min -sq.cm). Regional Gas Dose Ratio (RGDR): 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 adju st the exposure effect level for interspecies dosimetric differences to derive a hum an equivalent concentration for gases with respiratory effects. Relative Risk (or Risk Ratio (RR)): 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 m eans that the exposed group has twice the disease risk as the unexposed group. Reserve Volume: The volume of air remaining in the lungs after a m aximal expiration. Residual Volume (RV): The lung volume after maximal expiration (TLC - VC ). Risk (in the context of human health): The probability of adverse effects resulting from exposure to an environmental agent o r mixture of agents. Risk Assessment (in the context of human health): The evaluation of scientific information on the hazardous properties of environm ental agents (hazard characterization), the dose-response relationship ( dose-response assessment), and the extent of human exposure to those agents (expos ure assessment). The product of the risk assessment is a statement regarding theprobability that populations or individuals so exposed will be harmed and to what d egree (risk characterization). Risk Characterization: The integration of information on hazard, exposure , and dose-response to provide an estimate of the likelih ood that any of the identified adverse effects will occur in exposed people. 

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12/6/2011 http://www.epa.gov/NCEA/iris/help_gloss.htmRisk Management (in the context of human health): A decision making

process that accounts for political, social, econom ic and engineering implications together with risk-related information in order to develop, analyze and compare management options and select the appropriate manag erial response to a potential chronic health hazard. 

### S Short-Term Exposure: Repeated exposure by the oral, dermal, or inhalati on route for more than 24 hours, up to 30 days. Short-term Reference Concentration (RfC): An estimate (with uncertainty spanning perhaps an order of magnitude) of a contin uous inhalation exposure for short-term duration (up to 30 days) to the human po pulation (including sensitive subgroups) that is likely to be without an apprecia ble risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark concentration, with uncertainty factors generally a pplied to reflect limitations of the data used. Generally used in EPA's noncancer health assessments. Short-term Reference Dose (RfD): An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral expo sure 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 deleter ious 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 dat a used. Generally used in EPA's noncancer health assessments. Sigma g (s g): Geometric standard deviation. (See Mass Median Aerodynamic Diameter.) Slope Factor: An upper bound, approximating a 95% confidence limi t, on the increased cancer risk from a lifetime exposure to a n 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 o f the dose-response relationship, that is, for exposures corresponding to risks less than 1 in 100. Standardized Mortality Ratio (SMR): This is the relative measure of the difference in risk between the exposed and unexpose d populations in a cohort study. The SMR is similar to the relative risk in b oth definition and interpretation. This measure is usually standardized to control for any differences in age, sex, and/or race between the exposed and reference popul ations. It is frequently converted to a percent by multiplying the ratio by 100. Statistical Significance: The probability that a result is not likely to be due to chance alone. By convention, a difference between t wo groups is usually considered statistically significant if chance could explain i t only 5% of the time or less. Study design considerations may influence the a priori ch oice of a different level of statistical significance. Subchronic Exposure: Repeated exposure by the oral, dermal, or inhalati on route for more than 30 days, up to approximately 10% of t he life span in humans (more 

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12/6/2011 http://www.epa.gov/NCEA/iris/help_gloss.htmthan 30 days up to approximately 90 days in typical ly used laboratory animal

species). [See also longer-term exposure.] Subchronic Reference Concentration (RfC): An estimate (with uncertainty spanning perhaps an order of magnitude) of a contin uous inhalation exposure for a subchronic duration (up to 10% of average lifespan) to the human population (including sensitive subgroups) that is likely to b e without an appreciable risk of deleterious effects during a lifetime. It can be de rived from a NOAEL, LOAEL, or benchmark concentration, with uncertainty factors g enerally applied to reflect limitations of the data used. Generally used in EPA 's noncancer health assessments. Subchronic Reference Dose (RfD): An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral expo sure for a subchronic duration (up to 10% of average lifespan) to the human popula tion (including sensitive subgroups) that is likely to be without an apprecia ble 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 li mitations of the data used. Generally used in EPA's noncancer health assessment s. Subchronic Study: A toxicity study designed to measure effects from s ubchronic exposure to a chemical. Sufficient Evidence: A term used in evaluating study data for the class ification of a carcinogen under the 1986 U.S. EPA guidelines for carcinogen risk assessment. This classification indicates that there is a causa l relationship between the agent or agents and human cancer. Superfund: Federal authority, established by the Comprehensiv e Environmental Response, Compensation, and Liability Act (CERCLA) in 1980, to respond directly to releases or threatened releases of hazardous substa nces that may endanger health or welfare. Supporting Studies: Studies that contain information useful for provid ing insight and support for conclusions. Susceptibility: Increased likelihood of an adverse effect, often d iscussed in terms of relationship to a factor that can be used to des cribe a human subpopulation (e.g., life stage, demographic feature, or genetic charact eristic). Susceptible Subgroups: May refer to life stages, for example, children or the elderly, or to other segments of the population, fo r example, asthmatics or the immune-compromised, but are likely to be somewhat c hemical-specific and may not be consistently defined in all cases. Systemic Effects or Systemic Toxicity: Toxic effects as a result of absorption and distribution of a toxicant to a site distant from its entry point. 

### T Target Organ: The biological organ(s) most adversely affected byexposure to a chemical, physical, or biological agent. 

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12/6/2011 http://www.epa.gov/NCEA/iris/help_gloss.htmTeratogenic: Structural developmental defects due to exposure t o a chemical

agent during formation of individual organs. Threshold: The dose or exposure below which no deleterious effect is expected to occur. Tidal Volume (V T ): The volume of air inhaled/exhaled during normal bre athing. Total Lung Volume (TLV): The lung volume at maximal inspiration. Toxicity: Deleterious or adverse biological effects elicited by a chemical, physical, or biological agent. Toxicodynamics: The determination and quantification of the sequen ce of events at the cellular and molecular levels leading to a t oxic response to an environmental agent (sometimes referred to as pharmacodynamics). Toxicokinetics: The determination and quantification of the time c ourse of absorption, distribution, biotransformation, and ex cretion of chemicals (sometimes referred to as pharmacokinetics). Toxicology: The study of harmful interactions between chemical , physical, or biological agents and biological systems. Toxic Substance: A chemical, physical, or biological agent that maycause an adverse effect or effects to biological systems.
Tumor: An abnormal, uncontrolled growth of cells. Synonym : neoplasm Tumor Progression: Under the Armitage-Doll multistage theory of cance r development, the transition of a cell line between the stages which lead to cancer. Threshold Limit Value (TLV): Recommended guidelines for occupational exposure to airborne contaminants published by the American Conference of Governmental Industrial Hygienists (ACGIH). TLVs re present the average concentration in mg/m 3 for an 8-hour workday and a 40-hour work week to w hich nearly all workers may be repeatedly exposed, day a fter day, without adverse effect. 

### U Uncertainty: Uncertainty occurs because of a lack of knowledge. It is not the same as variability. For example, a risk assessor may bevery certain that different people drink different amounts of water but may be uncerta in about how much variability there is in water intakes within the population. Un certainty can often be reduced by collecting more and better data, whereas variabilit y is an inherent property of the population being evaluated. Variability can be bett er 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. 

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12/6/2011 http://www.epa.gov/NCEA/iris/help_gloss.htmUncertainty/Variability Factor (UFs): 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 i n susceptibility among the members of the human population (i.e., inter-indivi dual or intraspecies variability); (2) uncertainty in extrapolating animal data to hum ans (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 extrapol ation when the database is incomplete. Unit Risk: The upper-bound excess lifetime cancer risk estima ted to result from continuous exposure to an agent at a concentration of 1 μg/L in water, or 1 μg/m 3 in air. The interpretation of unit risk would be asfollows: 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: A plausible upper limit to the true value of a quan tity. This is usually not a true statistical confidence limit. 

### V Variability: Variability refers to true heterogeneity or divers ity. 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, differe nt exposure frequencies, and different exposure durations) as well as difference s in response (e.g., genetic differences in resistance to a chemical dose). Thos e inherent differences are referred to as variability. Differences among indiv iduals in a population are referred to as inter-individual variability, differences for one individual over time is referred to as intra-individual variability. Vital Capacity (VC): The maximum volume that can be exhaled in a single breath (TLC-RC). 

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### W

Weibull Model: A dose-response model of the form:

Weight-of-Evidence (WOE) for Carcinogenicity: A system used by the U.S. EPA for characterizing the extent to which the availabl e 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 evidenc e of noncarcinogenicity. The approach outlined in EPA's guidelines for carcinoge n 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 tha n categories. Five standard weight-of-evidence descriptors are used as part of the narrative. http://www.epa.gov/NCEA/iris/help_gloss.htm Last updated on Tuesday, July 26, 2011 

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