Related Terms
February 1, 1994
- Acceptable Daily Intake -- An estimate of the daily exposure dose that is likely to be without deleterious effect even if continued exposure occurs over a lifetime.
- Acute exposure -- One dose or multiple doses occurring within a short time (24 hours or less).
- Acute hazard or toxicity -- see Health hazard.
- Added risk -- The difference between the cancer incidence under the exposure condition and the background incidence in the absence of exposure;
- AR = P(d) - P(O).
- Aerodynamic diameter -- Term used to describe particles with common inertial properties to avoid the complications associated with the effects of particle size, shape and physical density.
- Anecdotal data -- Data based on descriptions of individual cases rather than on controlled studies.
- Attributable risk -- The difference between risk of exhibiting a certain adverse effect in the presence of a toxic substance and that risk in the absence of the substance.
- Benign -- Not malignant; remaining localized.
- Bioassay -- The determination of the potency (bioactivity) or concentration of a test substance by noting its effects in live animals or in isolated organ preparations, as compared with the effect of a standard preparation.
- Bioavailability -- The degree to which a drug or other substance becomes available to the target tissue after administration or exposure.
- Blood-to-air partition coefficient -- Ratio of concentrations for a given chemical achieved between blood and air at equilibrium.
- Carcinogen -- An agent capable of inducing a cancer response.
- Carcinogenesis -- The origin or production of cancer, very likely a series of steps. The carcinogenic event so modifies the genome and/or other molecular control mechanisms in the target cells that these can give rise to a population of altered cells.
- Case-control study -- An epidemiologic study that looks back in time at the exposure history of individuals who have the health effect (cases) and at a group who do not (controls), to ascertain whether they differ in proportion exposed to the chemical under investigation.
- Chronic effect -- An effect that is manifest after some time has elapsed from initial exposure. See also Health Hazard.
- Chronic exposure -- Multiple exposures occurring over an extended period of time, or a significant fraction of the animal's or the individual's life-time.
- Chronic hazard or toxicity -- see Health hazard.
- Chronic study -- A toxicity study designed to measure the (toxic) effects of chronic exposure to a chemical.
- Cohort study -- An epidemiologic study that observes subjects in differently exposed groups and compares the incidence of symptoms. Although ordinarily prospective in nature, such a study is sometimes carried out retro- spectively, using historical data.
- Confounder -- A condition or variable that may be a factor in producing the same response as the agent under study. The effects of such factors may be discerned through careful design and analysis.
- Control group -- A group of subjects observed in the absence of agent exposure or, in the instance of a case/control study, in the absence of an adverse response.
- Core grade(s) -- Quality ratings, based on standard evaluation criteria established by the Office of Pesticide Programs, given to toxicological studies after submission by registrants.
- Critical effect -- The first adverse effect, or its known precursor, that occurs as the dose rate increases.
- Developmental toxicity -- The study of adverse effects on the developing organism (including death, structural abnormality, altered growth, or func- tional deficiency) resulting from exposure prior to conception (in either parent), during prenatal development, or postnatally up to the time of sexual maturation.
- Dose-response relationship -- A relationship between the amount of an agent (either administered, absorbed, or believed to be effective) and changes in certain aspects of the biological system (usually toxic effects), apparently in response to that agent.
- Endpoint -- A response measure in a toxicity study. Estimated exposure dose (EED) -- The measured or calculated dose to which humans are likely to be exposed considering exposure by all sources and routes.
- Excess lifetime risk -- The additional or extra risk incurred over the lifetime of an individual by exposure to a toxic substance.
- Extra risk -- The added risk to that portion of the population that is not included in measurement of background tumor rate; ER(d) = [P(d) - P(O)]/ [1-P(O)].
- Extrapolation -- An estimation of a numerical value of an empirical (measured) function at a point outside the range of data which were used to calibrate the function. The quantitative risk estimates for carcinogens are generally low-dose extrapolations based on observations made at higher doses. Generally one has a measured dose and measured effect.
- Frank-effect level (FEL) -- Exposure level which produces unmistakable adverse effects, such as irreversible functional impairment or mortality, at a statistically or biologically significant increase in frequency or severity between an exposed population and its appropriate control.
- Gamma multi-hit model -- A dose-response model of the form P(d) = Integral from 0 to d of {[a**k][s**(k-1)][exp(-as)]/G(u)}ds where: G(u) = integral from 0 to infinity of [s**(u-1)][exp(-s)]ds P(d) = the probability of cancer from a dose rate d k = the number of hits necessary to induce the tumor a = a constant when k = 1, see the one-hit model.
- Guidelines for Carcinogen Risk Assessment -- U.S. EPA guidelines intended to guide Agency evaluation of suspect carcinogens in line with statutory pol- icies and procedures. See FR 33992-34003, September 24, 1986.
- Guidelines for Exposure Assessment -- U.S. EPA guidelines intended to guide Agency analysis of exposure assessment data in line with statutory pol- icies and procedures. See 51 FR 34042-34054, September 24, 1986.
- Guidelines for Health Assessment of Suspect Developmental Toxicants -- U.S. EPA guidelines intended to guide Agency analysis of developmental toxicity data in line with statutory policies and procedures. See 51 FR 34028-34040, September 24, 1986.
- Guidelines for the Health Risk Assessment of Chemical Mixtures -- U.S. EPA guidelines intended to guide Agency analysis of information relating to health effects data on chemical mixtures in line with statutory policies and proce- dures. See 51 FR 34014-34025, September 24, 1986.
- Guidelines for Mutagenicity Risk Assessment -- U.S. EPA guidelines intended to guide Agency analysis of mutagenicity data as related to heritable mutagenic risks, in line with statutory policies and procedures. See 51 FR 34006-34012, September 24, 1986.
- Health Advisory -- An estimate of acceptable drinking water levels for a chemical substance based on health effects information; a Health Advisory is not a legally enforceable Federal standard, but serves as technical guidance to assist Federal, state, and local officials.
- Health hazard (types of) --
- Acute toxicity: The older term used to describe immediate toxicty. Its former use was associated with toxic effects that were severe (e.g., mortality) in contrast to the term "subacute toxicity" that was associated with toxic effects that were less severe. The term "acute toxicity" is often confused with that of acute exposure.
- Allergic reaction: Adverse reaction to a chemical resulting from previous sensitization to that chemical or to a structurally similar one.
- Chronic toxicity: The older term used to describe delayed toxicity. However, the term "chronic toxicity" also refers to effects that persist over a long period of time whether or not they occur immediately or are delayed. The term "chronic toxicity" is often confused with that of chronic exposure.
- Idiosyncratic reaction: A genetically determined abnormal reactivity to a chemical.
- Immediate versus delayed toxicity: Immediate effects occur or develop rapidly after a single administration of a substance, while delayed effects are those that occur after the lapse of some time. These effects have also been referred to as acute and chronic, respectively.
- Reversible versus irreversible toxicity: Reversible toxic effects are those that can be repaired, usually by a specific tissue's ability to regenerate or mend itself after chemical exposure, while irreversible toxic effects are those that cannot be repaired.
- Local versus systemic toxicity: Local effects refer to those that occur at the site of first contact between the biological system and the toxicant; systemic effects are those that are elicited after absorption and distribution of the toxicant from its entry point to a distant site.
- Human equivalent concentration -- Exposure concentration for humans that has been adjusted for dosimetric differences between experimental animal species and humans to be equivalent to the exposure concentration associated with observed effects in the experimental animal species. If occupational human exposures are used for extrapolation, the human equivalent concentration represents the equivalent human exposure concentration adjusted to a continuous basis.
- Human equivalent dose -- The human dose of an agent that is believed to induce the same magnitude of toxic effect as that which the known animal dose has induced.
- Incidence -- The number of new cases of a disease within a specified period of time.
- Incidence rate -- The ratio of the number of new cases over a period of time to the population at risk.
- Individual risk -- The probability that an individual person will experi- ence an adverse effect. This is identical to population risk unless specific population subgroups can be identified that have different (higher or lower) risks.
- Initiation -- The ability of an agent to induce a change in a tissue which leads to the induction of tumors after a second agent, called a promoter, is administered to the tissue repeatedly. See also Promoter.
- Interspecies dose conversion -- The process of extrapolating from animal doses to equivalent human doses.
- Latency period -- The time between the initial induction of a health effect and the manifestation (or detection) of the health effect; crudely estimated as the time (or some fraction of the time) from first exposure to detection of the effect.
- Limited evidence -- According to the U.S. EPA's Guidelines for Carcinogen Risk Assessment, limited evidence is a collection of facts and accepted scien- tific inferences which suggests that the agent may be causing an effect, but this suggestion is not strong enough to be considered established fact.
- Linearized multistage procedure -- The modified form of the multistage model (see Multistage Model). The constant q1 is forced to be positive (>0) in the estimation algorithm and is also the slope of the dose-response curve at low doses. The upper confidence limit of q1 (called q1*) is called the slope factor.
- Logit model -- A dose-response model of the form P(d) = 1/[1 + exp -(a + b log d)] where P(d) is the probability of toxic effects from a continuous dose rate d, and a and b are constants.
- Lowest-observed-adverse-effect level (LOAEL) -- The lowest exposure level at which there are statistically or biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control group.
- Lowest-effect level (LEL) -- Same as LOAEL.
- Malignant -- Tending to become progressively worse and to result in death if not treated; having the properties of anaplasia, invasiveness, and metasta- sis.
- Margin of Exposure (MOE) -- The ratio of the no observed adverse effect level (NOAEL) to the estimated exposure dose (EED).
- Margin of Safety (MOS) -- The older term used to describe the margin of exposure.
- Mass median aerodynamic diameter (MMAD) -- Mass median of the distribution of mass with respect to aerodynamic diameter.
- Metastasis -- The transfer of disease from one organ or part to another not directly connected with it; adj., metastatic.
- Model -- A mathematical function with parameters which can be adjusted so that the function closely describes a set of empirical data. A "mathematical" or "mechanistic" model is usually based on biological or physical mechanisms, and has model parameters that have real world interpretation. In contrast, "statistical" or "empirical" models are curve-fitting to data where the math function used is selected for its numerical properties. Extrapolation from mechanistic models (e.g., pharmacokinetic equations) usually carries higher confidence than extrapolation using empirical models (e.g., logit).
- Modifying factor (MF) -- An uncertainty factor which is greater than zero and less than or equal to 10; the magnitude of the MF depends upon the profes- sional assessment of scientific uncertainties of the study and database not explicitly treated with the standard uncertainty factors (e.g., the complete- ness of the overall data base and the number of species tested); the default value for the MF is 1.
- Multistage model -- A dose-response model often expressed in the form P(d) = 1 - exp {-[q(0) + q(1)d + q(2)d**2 + ... + q(k)d**k]} where P(d) is the probability of cancer from a continuous dose rate d, the q(i) are the constants, and k is the number of dose groups (or, if less, k is the number of biological stages believed to be required in the carcinogenesis process). Under the multistage model, it is assumed that cancer is initiated by cell mutations in a finite series of steps. A one-stage model is equiva- lent to a one-hit model.
- No data -- According to the U.S. EPA Guidelines for Carcinogen Risk Assessment, "no data" describes a category of human and animal evidence in which no studies are available to permit one to draw conclusions as to the induction of a carcinogenic effect.
- No evidence of carcinogenicity -- According to the U.S. EPA Guidelines for Carcinogen Risk Assessment, a situation in which there is no increased inci- dence of neoplasms in at least two well-designed and well-conducted animal studies of adequate power and dose in different species.
- No-observed-adverse-effect level (NOAEL) -- An exposure level at which there are no statistically or biologically significant increases in the frequency or severity of adverse effects between the exposed population and its appropriate control; some effects may be produced at this level, but they are not considered as adverse, nor precursors to adverse effects. In an experiment with several NOAELs, the regulatory focus is primarily on the highest one, leading to the common usage of the term NOAEL as the highest exposure without adverse effect.
- 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.
- One-hit model -- A dose-response model of the form P(d) = a - exp(-b d) where P(d) is the probability of cancer from a continuous dose rate d, and b is a constant. The one-hit model is based on the concept that a tumor can be induced after a single susceptible target or receptor has been exposed to a single effective dose unit of a substance.
- Organoleptic -- Affecting or involving a sense organ as of taste, smell, or sight.
- Physiologically based pharmacokinetic (PBPK) model -- Physiologically based compartmental model used to quantitatively describe pharmacokinetic behavior.
- Principal study -- The study that contributes most significantly to the qualitative and quantitative risk assessment.
- Probit model -- A dose-response model of the form P(d) = 0.4{integral from minus infinity to [log(d - u)]/s of [exp-(y**2)/2]dy} where P(d) is the probability of cancer from a continuous dose rate d, and u and s are constants.
- Promoter -- In studies of skin cancer in mice, an agent which results in an increase in cancer induction when administered after the animal has been exposed to an initiator, which is generally given at a dose which would not result in tumor induction if given alone. A cocarcinogen differs from a pro- moter in that it is administered at the same time as the initiator. Cocarcin- ogens and promoters do not usually induce tumors when administered separately. Complete carcinogens act as both initiator and promoter. Some known promoters also have weak tumorigenic activity, and some also are initiators. Carcinogens may act as promoters in some tissue sites and as initiators in others.
- Proportionate mortality ratio (PMR) -- The number of deaths from a spe- cific cause and in a specific period of time per 100 deaths in the same time period.
- Prospective study -- A study in which subjects are followed forward in time from initiation of the study. This is often called a longitudinal or cohort study.
- q1* -- Upper bound on the slope of the low-dose linearized multistage procedure.
- 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 noncancer effects during a lifetime.
- Reference Dose (RfD) -- An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime.
- Regional deposited dose (RDD) -- The deposited dose of particles calculated for the region of interest as related to the observed effect. 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 extrarespiratory 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 (RGD) -- 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.
- Registration (of a pesticide) -- Under FIFRA and its amendments, new pesticide products cannot be sold unless they are registered with the U.S. EPA. Registration involves a comprehensive evaluation of risks and benefits based on all relevant data.
- Regulatory dose (RgD) -- The daily exposure to the human population reflected in the final risk management decision; it is entirely possible and appropriate that a chemical with a specific RfD may be regulated under differ- ent statutes and situations through the use of different RgDs.
- Relative risk (sometimes referred to as risk ratio) -- The ratio of incidence or risk among exposed individuals to incidence or risk among nonexposed individuals.
- Reportable quantity -- The quantity of a hazardous substance that is con- sidered reportable under CERCLA. Reportable quantities are: (1) one pound, or (2) for selected substances, an amount established by regulation either under CERCLA or under Section 311 of the Clean Water Act. Quantities are measured over a 24-hour period.
- Risk -- The probability of injury, disease, or death under specific cir- cumstances. In quantitative terms, risk is expressed in values ranging from zero (representing the certainty that harm will not occur) to one (representing the certainty that harm will occur). The following are examples showing the manner in which risk is expressed in IRIS: E-4 = a risk of 1/10,000; E-5 = a risk of 1/100,000; E-6 = a risk of 1/1,000,000. Similarly, 1.3E-3 = a risk of 1.3/1000 = 1/770; 8E-3 = a risk of 1/125; and 1.2E-5 = a risk of 1/83,000.
- Risk assessment -- The determination of the kind and degree of hazard posed by an agent, the extent to which a particular group of people has been or may be exposed to the agent, and the present or potential health risk that exists due to the agent.
- Risk management -- A decisionmaking process that entails considerations of political, social, economic, and engineering information with risk-related information to develop, analyze, and compare regulatory options and to select the appropriate regulatory response to a potential chronic health hazard.
- Safety Factor -- See Uncertainty Factor. Short-term exposure -- Multiple or continuous exposures occurring over a week or so.
- Slope Factor -- The slope of the dose-response curve in the low-dose region. When low-dose linearity cannot be assumed, the slope factor is the slope of the straight line from 0 dose (and 0 excess risk) to the dose at 1% excess risk. An upper bound on this slope is usually used instead of the slope itself. The units of the slope factor are usually expressed as 1/(mg/kg-day).
- Standardized mortality ratio (SMR) -- The ratio of observed deaths to expected deaths.
- Subchronic exposure -- Multiple or continuous exposures occurring usually over 3 months.
- Subchronic study -- A toxicity study designed to measure effects from sub- chronic exposure to a chemical.
- Sufficient evidence -- According to the U.S. EPA's Guidelines for Carcin- ogen Risk Assessment, sufficient evidence is a collection of facts and scien- tific references which is definitive enough to establish that the adverse effect is caused by the agent in question.
- Superfund -- Federal authority, established by the Comprehensive Environ- mental 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 -- Those studies that contain information that is useful for providing insight and support for the conclusions.
- Systemic effects -- Systemic effects are those that require absorption and distribution of the toxicant to a site distant from its entry point, at which point effects are produced. Most chemicals that produce systemic toxicity do not cause a similar degree of toxicity in all organs, but usually demonstrate major toxicity to one or two organs. These are referred to as the target organs of toxicity for that chemical.
- Systemic toxicity -- See Systemic effects.
- Target organ of toxicity -- See Systemic effects.
- Threshold -- The dose or exposure below which a significant adverse effect is not expected. Carcinogens are thought to be non-threshold chemicals, to which no exposure can be presumed to be without some risk of adverse effect.
- Threshold Limit Values (TLVs) -- Recommended guidelines for occupational exposure to airborne contaminants published by the American Conference of Governmental Industrial Hygienists (ACGIH). The TLVs represent the average concentration (in mg/cu.m) 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.
- Tumor progression -- The sequence of changes in which a tumor develops from a microscopic lesion to a malignant stage.
- Uncertainty factor -- One of several, generally 10-fold factors, used in operationally deriving the Reference Dose (RfD) from experimental data. UFs are intended to account for (1) the variation in sensitivity among the members of the human population; (2) the uncertainty in extrapolating animal data to the case of humans; (3) the uncertainty in extrapolating from data obtained in a study that is of less-than-lifetime exposure; and (4) the uncertainty in using LOAEL data rather than NOAEL data.
- Unit Risk -- The upper-bound excess lifetime cancer risk estimated to result from continuous exposure to an agent at a concentration of 1 ug/L in water, or 1 ug/cu.m in air.
- Upper bound -- An estimate of the plausible upper limit to the true value of the quantity. This is usually not a statistical confidence limit.
- Weibull model -- A dose-response model of the form P(d) = 1 - exp [-b(d**m)] where P(d) is the probability of cancer due to continuous dose rate d, and b and m are constants.
- Weight-of-evidence for carcinogenicity -- The extent to which the avail-
able biomedical data support the hypothesis that a substance causes cancer
in
humans.
Last updated: 20 February 1998
URL: http:/www.epa.gov/iris/GLOSSARY.HTM