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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 not included in this glossary, the 

user should refer to standard health science, biostatistics 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 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. 

Integrated Risk Information System (IRIS)

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Acute 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 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. 

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 Difference) (AR): 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. 

Adverse Effect: 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: 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: 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-body-weight basis. The ADD is 

usually expressed in terms of mg/kg-day or other mass-time units. 

B 

Background Levels: 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, 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 or concentration at 

the BMD or BMC, respectively. 

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Benchmark Response (BMR): 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. 

Benign Tumor: 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: An assay for determining the potency (or concentration) of a substance 

that causes a biological change in experimental animals. 

Bioavailability: The degree to which a substance becomes available to 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 (CASRN) 

is an unique numeric identifier, designed to designate only one substance so it can 

be referenced by many Government Agencies and/or internationally. 

Cancer: A disease of heritable, somatic mutations affecting cell growth and 

differentiation, characterized by an abnormal, uncontrolled 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 population of altered cells. 

Case-control Study: 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: An effect that occurs as a result of repeated or long term (chronic) 

exposures. 

Chronic Exposure: 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 (RfC): 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) 

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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.

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 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.

Chronic Study: A toxicity study designed to measure the (toxic) effects 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 exposure. These two cohorts are 

then followed over time to determine the differences 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 interest is associated with disease. 

Control Group (or Reference Group): 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: 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: 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: The study that contributes most significantly to the qualitative and 

quantitative assessment of risk. Also called Principal Study. 

D

Developmental Toxicity: Adverse effects on the developing organism that may

result from exposure prior to conception (either parent), during prenatal 

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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: 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: 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: 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). 

E

Effective Dose (ED10): The dose corresponding to a 10% increase in an adverse 

effect, relative to the control response. 

Endpoint: 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: 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 sources 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 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: 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. 

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Extra Risk (ER): 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. 

Extrapolation, low dose: An estimate of the response at a point below the range 

of the experimental data, generally through the use of a mathematical model. 

F

Forced Expiratory Volume (FEV1): The volume of air that can be forcibly exhaled 

during the first second of expiration following a maximal inspiration. 

Forced Vital Capacity (FVC): The maximal volume of air that can be exhaled as 

forcibly and rapidly as possible after a maximal inspiration. 

Frank Effect Level (FEL): 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. 

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 definition) 

for low-dose extrapolation. The probability P(d) that 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. EPA guidelines 

intended to guide Agency evaluation of suspect carcinogens. 66 FR 

17765-17817, April 7, 2005.

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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. 

H

Hazard: A potential source of harm. 

Hazard Assessment: 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: 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 (HEC) or Dose (HED): 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. 

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 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 

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per 1,000,000 people if exposed daily for a lifetime to 1 μg of the chemical per m3

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 manifestation or 

detection of a health effect of interest. 

Limited Evidence: 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: 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 extrapolation, of the 

form: 

Longer-Term Exposure: 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 Dose10 (LED10): 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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Lowest-Observed-Effect Level (LOEL or LEL): 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. 

M

Malignant Tumor: An abnormal growth of tissue which can invade adjacent or 

distant tissues. 

Margin of Exposure (MOE): The LED10 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 aerodynamic diameter. MMADs are 

usually accompanied by the geometric standard deviation (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 parameter most likely to have 

produced the sample observations. 

Metastasis: The dissemination or secondary growth of a malignant 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 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 (MF): 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.]

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 (of exposures) in the population. 

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Multistage Model: A mathematical function used to extrapolate the probability of 

cancer from animal bioassay data, using the form: 

Multistage Weibull Model: A dose-response model for low-dose extrapolation that 

includes a term for decreased survival time associated with tumor incidence: 

Mutagen: A substance that can induce an alteration in the structure 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 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. 

No-Observed-Effect Level (NOEL): 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. 

Non-Linear Dose Response: A pattern of frequency or severity of biological 

response that does not vary directly with the amount of dose of an agent. 

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O

Odds Ratio (OR): 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. 

Oncogenic: 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: 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. 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 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: Affecting or involving a sense organ such as that of taste, smell, or 

sight. 

P

Physiologically Based Pharmacokinetic (PBPK) Model: 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. 

Point of Departure: The dose-response point that marks the beginning of a lowdose 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: A unit of measure expressed as parts per billion. Equivalent to 1 x 10-9. 

ppm: A unit of measure expressed as parts per million. Equivalent 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 individuals within that population at 

the same point in time. 

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Probit 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 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. 

Prospective Study: See cohort study. 

R

Reference Concentration (RfC): 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].

Reference Dose (RfD): 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]. 

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 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 

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numerical 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 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). 

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. This ratio is used to adjust the 

exposure effect level for interspecies dosimetric differences 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 deposited dose is adjusted for 

ventilatory volumes and the surface area of the respiratory 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 adjust the exposure effect level for 

interspecies dosimetric differences to derive a human 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 means 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 maximal 

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 or mixture of agents. 

Risk Assessment (in the context of human health): 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: 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. 

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Risk Management (in the context of human health): 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. 

S

Short-Term Exposure: Repeated exposure by the oral, dermal, or inhalation 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 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.

Short-term Reference Dose (RfD): 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. 

Sigma g (s g): Geometric standard deviation. (See Mass Median Aerodynamic 

Diameter.) 

Slope Factor: 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 (SMR): 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. 

Statistical Significance: 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: 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 

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than 30 days up to approximately 90 days in typically 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 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. 

Subchronic Reference Dose (RfD): 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. 

Subchronic Study: A toxicity study designed to measure effects from subchronic 

exposure to a chemical. 

Sufficient Evidence: 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: 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: Studies that contain information useful for providing insight 

and support for conclusions. 

Susceptibility: 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: 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 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 by exposure to a 

chemical, physical, or biological agent. 

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Teratogenic: Structural developmental defects due to exposure to a chemical 

agent during formation of individual organs. 

Threshold: The dose or exposure below which no deleterious effect is expected to 

occur. 

Tidal Volume (VT): The volume of air inhaled/exhaled during normal breathing. 

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 sequence of events 

at the cellular and molecular levels leading to a toxic response to an environmental 

agent (sometimes referred to as pharmacodynamics).

Toxicokinetics: The determination and quantification of the time course of 

absorption, distribution, biotransformation, and excretion 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 may cause 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 cancer 

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 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. 

U

Uncertainty: 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.

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Uncertainty/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 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. 

Unit Risk: 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: A plausible upper limit to the true value of a quantity. This is usually 

not a true statistical confidence limit. 

V

Variability: 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.

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 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.

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Last updated on Tuesday, July 26, 2011

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