Glossary of key terms associated with environmental toxicology
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Absorption: Uptake of the chemical from the site of administration / site of exposure into the general circulation. Absorption may involve a number of stages (e.g., dissolution) and diffusion through membranes. Chemicals may be changed during absorption due to metabolism or degradation, such that it is possible to have complete absorption and low bioavailability.
Acceptable daily intake (ADI): Amount of exposure determined to be "safe"; usually derived from the lowest No Effect Level in an experimental study, divided by a safety factor such as 100. Also known as the Reference Dose (RfD).
Acceptable risk: A risk that is so low that no significant potential for toxicity exists, or a risk society considers is outweighed by benefits.
Accumulation: This is the build-up of chemical in the organism as a result of repeated or long-term exposure.
Accumulative effect of a chemical: The effect of a chemical on a biologic system when the chemical has been administered at a rate that exceeds its elimination from the system. Sufficient accumulation of the chemical in the system can lead to toxicity.
Acetylation: The addition of an acetyl group from acetyl coenzyme A to a xenobiotic or xenobiotic metabolite by the enzyme N-acetyltransferase. Polymorphisms in this enzyme can be important in the expression of toxicity in humans.
Acid deposition:(1) Wet and dry air pollutants that lower the pH of deposition and subsequently the pH of the environment. Acid rain with a pH of 4 or lower refers to the wet components. Normal rain has a pH of about 5.6. Sulphuric acid from sulphur and nitric acid from nitrogen oxides are the major contributors. In lakes in which the buffering capacity is low, the pH becomes acidic enough to cause fish kills, and the lakes cannot support fish populations. A contributing factor is the fact that acidic conditions concurrently release toxic metals, such as aluminum, into the water. (2) Acidic material that falls from the atmosphere to the earth in either wet (rain, sleet, snow, or fog) or dry (gases and particles) forms.
Acidic pollutants: Harmful particles, such as sulphur dioxide and nitrogen oxides, that turn into acid when they mix with water and oxygen in the sky.
Activation (bioactivation): In toxicology, this term is used to describe metabolic reactions of a xenobiotic in which the product is more toxic than is the substrate. Such reactions are most commonly monooxygenations, the products of which are electrophiles that, if not detoxified by Phase II (conjugation) reactions, may react with nucleophilic groups on cellular macromolecules such as proteins and DNA.
Active oxygen: Term used to describe various short-lived highly reactive intermediates in the reduction of oxygen. Active oxygen species such as superoxide anion and hydroxyl radical are known or believed to be involved in several toxic actions. Superoxide anion is detoxified by superoxide dismutase.
Acute: Characterized by a time period of short duration; commonly used to describe single-dose exposure in toxicity studies.
Acute-to-chronic ratio (ACR): A ratio determined experimentally or mathematically for a chemical that is used to predict chronic toxicity when only acute toxicity data are available.
Acute toxicity: Refers to adverse effects on, or mortality of, organisms following soon after a brief exposure to a chemical agent. Either a single exposure or multiple exposures within a short time period may be involved, and an acute effect is generally regarded as an effect that occurs within the first few days after exposure, usually less than 2 weeks.
Acute toxicity study: Usually, a single-dose study in which animals are observed for a 2-week period postdose to determine overt signs of toxicity, normally including some form of assessment of the lethal dose.
Acute toxicity tests: The most common tests for acute toxicity are the LC50 and LD50 tests, which are designed to measure mortality in response to an acute toxic insult. Other tests for acute toxicity include dermal irritation tests, dermal sensitization tests, eye irritation tests, photoallergy tests, and phototoxicity tests.
Adaptation to toxicants: Refers to the ability of an organism to show insensitivity or decreased sensitivity to a chemical that normally causes deleterious effects. The terms resistance and tolerance are closely related and have been used in several different ways. However, a consensus is emerging to use the term resistance to mean that situation in which a change in the genetic constitution of a population in response to the stressor chemical enables a greater number of individuals to resist the toxic action than were able to resist it in the previous unexposed population. Thus, an essential feature of resistance is selection and then inheritance by subsequent generations. In microorganisms, this frequently involves mutations and induction of enzymes by the toxicant; in higher organisms, it usually involves selection for genes already present in the population at low frequency. The term tolerance is then reserved for situations in which individual organisms acquire the ability to resist the effect of a toxicant, usually as a result of prior exposure.
Adsorption: The process by which chemicals become attached to solid surfaces.
Air pollution: In general, the principal air pollutants are carbon monoxide, oxides of nitrogen, oxides of sulphur, hydrocarbons, and particulates. The principal sources are industrial processes, transportation, electric power generation, and the heating of buildings. Hydrocarbons such as benzo(a)pyrene are produced by incomplete combustion and are associated primarily with the automobile. They are usually not present at levels high enough to cause direct toxic effects but are important in the formation of photochemical air pollution, formed as a result of interactions between oxides of nitrogen and hydrocarbons in the presence of ultraviolet light, giving rise to lung irritants such as acrolein, peroxyacetyl nitrate, and formaldehyde. Particulates are a heterogeneous group of particles, often seen as smoke, that are important as carriers of absorbed hydrocarbons and as irritants to the respiratory system.
Alkaline chemicals: Substances that cause an object to become less acidic when they come into contact with each other.
Allergen: A substance causing an allergic reaction.
Anoxia: A complete reduction in the oxygen concentration supplied to cells or tissues.
Anthropogenic: Produced or caused by the actions of humans.
Aquatic toxicology: The study of adverse effects on freshwater and saltwater biota and on the ecosystems that contain them.
Assessment endpoint: An ecological value representing the focus for protection in an ecological risk assessment.
Auto-oxidation (or weathering): Commonly used to describe the general oxidative degradation of a chemical (or chemical mixture such as petroleum) upon exposure to air.
Bioaccumulation: The accumulation of a chemical within the tissue of an organism either from the medium (usually water) directly or from consumption of food containing the chemical.
Bioaccumulation factor (BAF): The ratio of chemical concentration in an organism of interest to the concentration in its exposure medium.
Bioactivation: See activation.
Bioassay: A toxicity study in which specific toxic effects from chemical exposure are measured in the laboratory using living organisms.
Bioavailability: The fraction (or sometimes percentage) of the dose that enters the general circulation as the parent compound. A low bioavailability may be due to poor absorption or first-order conditions; the state of being capable of being absorbed and available to interact with the metabolic processes of an organism. Bioavailability is typically a function of chemical properties, physical state of the material to which an organism is exposed, and the ability of the individual organism to physiologically take up the chemical.
Bioconcentration: The accumulation of a substance that partitions from water to an organism, assuming steady-state conditions. Often used to describe body burdens in aquatic organisms, can also be used for terrestrial organisms that experience exposure through soil pore water transfer.
Bioconcentration factor (BCF): The tendency of a chemical to be more concentrated in an aquatic organism than the concentration in its environment, calculated by dividing the concentration of the chemical in the organism (wet weight) by the concentration of the chemical in the water.
Biodegradation: The breakdown of the chemical into simpler compounds primarily by microorganisms. Does not apply to inorganic compounds.
Biodiversity: The variety of organisms considered at all levels, from genetic variants belonging to the same species through arrays of species to arrays of genera, families, and higher taxa; includes the variety of ecosystems that comprise both the communities of organisms within particular habitats and the physical conditions under which they live.
Biological half-life: The time required for the concentration of a chemical present in the body or in a particular body compartment to decrease by one-half through biological processes such as metabolism and excretion.
Biologically effective dose: The amount of a deposited or absorbed chemical that reaches the cells or target site where an adverse effect occurs or where that chemical interacts with a membrane surface.
Biomagnification: The increasing concentration of a substance in organism tissues at successively higher trophic levels that occurs through trophic transfer, that is, ingestion of food items (dietary accumulation).
Biomarker: Observable change (not necessarily pathological) in the function of an organism, related to a specific exposure or event; a biochemical, genetic, or molecular indicator that can be used to screen disease or toxicity; parameters that can be used as an indicator of exposure, effect, or susceptibility and may be a metabolite, enzyme, or cell surface marker, among others.
Biotransformation: The biochemical modification of a xenobiotic once it enters an organism. Chemical modification can be enzymatic or nonenzymatic and may result in either reduced or increased toxicity. This process generally gives rise to compounds that are more readily excreted in the urine and feces and thus serves as a detoxification process; however, some xenobiotics are activated to more toxic metabolites by these enzymatic conversions.
Carcinogen: A chemical capable of inducing cancer.
Carcinogenesis: This is the process encompassing the conversion of normal cells to neoplastic cells and the further development of these neoplastic cells into a tumor. This process results from the action of specific chemicals, certain viruses, or radiation. Chemical carcinogens have been classified into those that are genotoxic and those that are epigenetic (i.e., not genotoxic).
CAS Number: Abbreviation for Chemical Abstracts Service Registry Number. This is a universal number that is assigned to a specific compound. It is used to overcome any problems in nomenclature or language.
Chronic: Characterized by a time period of long duration; commonly used to describe long-term (6-12 months) exposure in toxicity studies.
Chronic toxicity: This term is used to describe adverse effects manifested after a long time period of uptake of small quantities of the toxicant in question. The dose is small enough that no acute effects are manifested, and the time period is frequently a significant part of the expected normal lifetime of the organism. The most serious manifestation of chronic toxicity is carcinogenesis, but other types of chronic toxicity are also known (e.g., reproductive effects, behavioral effects).
Chronic toxicity study: A multiple-dose study in which animals are treated for a period ≥ 6 months to comprehensively assess the potential toxicological effects of a compound following long-term exposure; normally, these studies are required prior to phase II testing in humans.
Chronic toxicity tests: Chronic tests are those conducted over a significant part of the life span of the test species or, in some cases, more than one generation. The most important tests are carcinogenicity tests, and the most common test species are rats and mice.
Community: Groups of different populations that coexist, within some defined geographical location, and which interact with each other.
Comparative toxicology: The study of the variation in the expression of the toxicity of exogenous chemicals toward organisms of different taxonomic groups or of different genetic strains.
Compartment: In pharmaco(toxico)kinetics, a compartment is a hypothetical volume of an animal system wherein a chemical acts homogeneously in transport and transformation. These compartments do not correspond to physiological or anatomic areas but are abstract mathematical entities useful for predicting drug or toxicant concentrations. Transport into, out of, or between compartments is described by rate constants, which are used in models of the intact animal.
Control group: This is a group of experimental organisms that are no exposed to the treatment or chemical used in the main test. They are compared to the exposed experimental groups in order to observe whether the resulting effects in the experimental groups are significant.
Cumulative exposure: A summation of all the exposures that have been undergone by an organism during a specified period of time.
Cytochrome P450: A group of structurally related enzymes comprising the mixed function oxidase (MFO) system; responsible for initial metabolism of a wide variety of foreign chemicals.
Degradable: Can be broken down into simpler structures.
Dermal contact: Exposure to a chemical through the skin.
Detoxication: A metabolic reaction or sequence of reactions that reduces the potential for adverse effect of a xenobiotic. Such sequences normally involve an increase in water solubility that facilitates excretion and/or the reaction of a reactive product with an endogenous substrate (conjugation), thereby not only increasing water solubility but also reducing the possibility of interaction with cellular macromolecules. Not to be confused with detoxification. See also Detoxification.
Detoxification: The metabolic process by which the toxic qualities of a poison or toxin are reduced by the body. Not to be confused with detoxication. See also Detoxication.
Developmental toxicity: Adverse effects on the developing organism. Adverse developmental effects may be detected at any point in the life span of the organism. Major manifestations of developmental toxicity include: death of the developing organism, induction of structural abnormalities (teratogenicity), altered growth, and functional deficiency.
Disposition: Unlike absorption, disposition consists not just of one kind of process but, rather, of a number of different kinds of processes taking place simultaneously. Disposition includes both distribution and elimination, which occur in parallel in almost all cases and are often considered independently of each other.
Distribution: The term distribution refers both to the movement of a toxicant from the portal of entry to the tissue and also to the description of the different concentrations reached in different locations. The first involves the study of transport mechanisms primarily in the blood, and both are subject to mathematical analysis in toxicokinetic studies.
DNA: Deoxyribonucleic acid.
Dosage: The amount of a toxicant, drug, or other chemical administered or taken expressed as some function of the organism (e.g., mg/kg body, weight/day).
Dose: The amount of a substance available for interaction 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 of a substance 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 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 dose for that organ or cell.
In toxicity studies, dose is the quantity of a chemical administered to experimental animals at specific time intervals. The quantity can be further defined in terms of quantity per unit weight or per body surface area of the test animal. Sometimes the interval of time over which the dose is administered is part of the dose terminology. Examples are: grams (or milligrams) per kilogram of body weight (or per square meter of body surface area).
Dose-response assessment: A step in the risk assessment process to characterize the relationship between the dose of a chemical administered to a population of test animals and the incidence of a given adverse effect. It involves mathematical modeling techniques to extrapolate from the high dose effects observed in test animals to estimate the effects expected from exposure to the typically low doses that may be encountered by humans.
Dose-response model: A mathematical expression that relates the incidence or magnitude of a biological effect to the dose of a chemical.
Dose-response relationship: One of the most basic principles of toxicology. It states that the intensity of responses elicited by a chemical is a function of the administered dose (i.e., a larger dose produces a greater effect than a smaller dose, up to the limit of the capacity of the biologic system to respond).
Ecological risk assessment: The process used to establish the likelihood that adverse ecological effects are occurring or may occur as a result of exposure to one or more stressors.
Ecosystem: The sum total of all interactions linking organisms in a community with each other and their environment. Comprises different communities along with the physical/chemical environment. Exampes include forest ecossystems, aquatic ecossystems such as streams, lakes, etc.
Ecotoxicology: "The field of study which integrates the ecological and toxicological effects of chemical pollutants on populations, communities and ecosystems with the fate (transport, transformation and breakdown) of such pollutants in the environment" (Forbes and Forbes, 1994)*. See also Environmental toxicology.
- * FORBES VE. FORBES TL. 1994. ECOTOXICOLOGY IN THEORY AND PRACTICE. CHAPMAN AND HALL, LONDON, 247PP.
Effect concentration (EC): Concentration of a substance in media predicted to cause a measurable change in a defined proportion (e.g., 50%) of a population of organisms.
Effective concentration-50% (EC50): A statistically or graphically determined concentration of a chemical that reduces a sublethal response parameter of interest by 50%. Also known as Median effective concentration.
Effective dose-50% (ED50): The dose of a particular substance that elicits an observable response in 50% of the test subjects. The ED50 is expressed in terms of weight of test substance per unit weight of test animal (mg/kg). Also known as Median effective dose.
EINECS: European Inventory of Existing Commercial Chemical Substances. All existing substances on the European market in the 10-year period to September 1981 were put on an inventory. It excluded polymers and contains approximately 100,000 substances; all called by their proper chemical name together with the CAS and EINECS numbers.
Elimination: (1) The removal of a chemical substance from the body. The rate of elimination depends on the nature of the chemical and the mechanisms that are used to remove the chemical from the organism. Examples of mechanisms include expiration from the lungs, excretion by the kidneys by way of the urinary system, excretion in the sweat or saliva, and chemical alteration by the organism and subsequent excretion by any of these mechanisms. (2) The irreversible transfer of the chemical from circulation to the organs of elimination and its subsequent removal from the body by metabolism or excretion.
ELINCS: European List of Notified Chemical Substances.
Endocrine disruptors: An endocrine disruptor is an exogenous chemical that interacts with the endocrine system of an organism to produce one or more deleterious effects. These effects may be brought about in a number of ways including serving as ligands for hormone receptors and inhibition or induction of hormone-metabolizing enzymes.
Endpoint: A specific biological effect or response which is used as an indicator of the effect of a chemical on the organism. For example, lethality or a change in enzyme function, etc. can be endpoints.
Environment: The Collins English Dictionary defines environment as 'the external surroundings in which a plant or animal lives, which tend to influence its development and behaviour'. Taking into account a more detailed view, the environment is composed of both a living component, or biota, which includes animals, plants, humans, etc., and a non-living component, or abiota, such as air, water, soil, etc., and each component interacts with the other in a variety of ways.
Environmental chemistry: It is the study of the chemical and biochemical occurrences in natural places. It is an interdisciplinary science that includes atmospheric, aquatic and soil chemistry, as well as the study of chemical processes occurring in the environment which are impacted by humankind's activities. Environmental chemistry involves first understanding how the uncontaminated environment works, which chemicals (in what concentrations) are present naturally, and with what effects.
Environmental contaminants: Refers to harmful chemicals present in soil, air and water. These compounds may come directly from human sources such as industrial manufacturing, agricultural runoff and wastewater discharge, or they may originate from natural sources, such as the taste and odor-causing chemicals in water generated by algae and bacteria blooms.
Environmental fate: The final destination of a chemical once it has been released into the environment. Aspects such as transport in the different environmental compartments have to be taken into consideration as well as bioaccumulation potential and persistence. Thus, environmental fate involves temporal and spatial considerations of transport, transfer, storage, and transformation.
Environmental toxicology: This is concerned with the movement of toxicants and their metabolites in the environment and in food chains and the effect of such toxicants on populations of organisms. See also Ecotoxicology.
Enzyme: A protein that increases the rate of a metabolic reaction.
EPA: Environmental Protection Agency.
Epigenetic: Alterations in the expression of genes by mechanisms other than changes in the nucleotide sequence of DNA.
Excretion: The process whereby materials are removed from the body to the external environment. If a chemical is in solution as a gas at body temperature, it will appear in the air expired from the animal; if it is a nonvolatile substance, it may be eliminated by the kidney via the urinary system, or it may be chemically altered by the animal and then excreted by means of any of the mechanisms available to the animal, such as excretion in the urine, in the sweat, or in the saliva.
Exposure: Contact of a chemical, physical, or biological substance with the outer boundary of an organism. Exposure is quantified as the concentration of the agent in the medium in contact integrated over the time duration of contact.
Exposure assessment: A component of human health risk assessment. The determination or estimation (qualitative or quantitative) of the magnitude, frequency, duration and route of exposure. The exposure assessment also describes the nature of exposure and the size and nature of the exposed populations.
Exposure characterization: The component of an ecological risk assessment in which exposure is evaluated. This is parallel to the exposure assessment component of a human health risk assessment.
Exposure concentration: The concentration of a chemical in its transport or carrier medium at the point of contact.
Exposure duration: The number of years a receptor is exposed to a chemical. This can be either a measured or assumed value.
Exposure frequency: (1) The number of days per year a receptor is exposed to a chemical. This can be either a measured or assumed value. (2) The number of times an exposure occurs in a given period. The exposure(s) may be continuous, discontinuous but regular (e.g., once daily), or intermittent.
Exposure medium: A matrix (e.g., soil, water, air) in which an organism contacts with a chemical.
Exposure pathway: The physical course a chemical or pollutant takes from the source to the organism exposed.
Exposure point: A location where a receptor is exposed to a chemical. This can be either a known or assumed location.
Exposure profile: The product of the exposure characterization component of an ecological risk assessment in which exposure is estimated or measured.
Exposure route: The way in which a chemical enters an organism after contact (i.e., by inhalation, ingestion, or dermal absorption).
Extrapolation: An estimate of response or quantity at a point outside the range of the experimental data. Also refers to the estimation of a measured response in a different species or by a different route than that used in the experimental study of interest (i.e., species-to- species, route-to-route, acute-to-chronic, high-to-low).
First-pass effect: (1) Chemical transformation in the liver following absorption from the gastrointestinal tract prior to release of the chemical to other locations. (2) Reduction in a substance's systemic availability resulting from metabolism or excretion by the first major organ of contact with such capability after the absorption process. This phenomenon is often associated with the lung or liver.
Fossil fuels: Substances found below the surface of the earth that can be burned to create energy. The three primary fossil fuels are coal, oil, and natural gas.
G
Genomics: The distinction (sometimes stated) that genomics deals with genomes while molecular biology deals with single genes is unrealistic and unnecessary; it is more appropriate to regard genomics as an aspect of molecular biology that deals not only with genomes and gene expression but also such important aspects as genetic polymorphisms, particularly single nucleotide polymorphisms (SNPs). Techniques, such as microarrays, are now available to examine simultaneously the expression of very large numbers of genes.
Genotoxic: A broad term that usually refers to a chemical which has the ability to damage DNA or the chromosomes. This can be determined directly by measuring mutations or chromosome abnormalities or indirectly by measuring DNA repair, sister-chromatid exchange, etc.
Genotoxic carcinogens: Cancer-causing agents that exert their carcinogenic effect by a series of events that is initiated by an interaction with DNA, either directly or through an electrophilic metabolite.
GI: Gastrointestinal.
Grey list: List 2 annexed to EEC Directive 76/464/EEC that includes compounds such as certain biocides, heavy metals, cyanides and fluorides. Pollution by these compounds must be reduced.
Hazard: The inherent property of a single chemical or mixture to cause adverse effects under defined conditions of exposure; the potential for an adverse health or ecological effect.
Hazard identification: Considered the first step in risk assessment, hazard identification involves the qualitative determination of whether exposure to a chemical causes an increased incidence of an adverse effect, such as cancer or birth defects, in a population of test animals and an evaluation of the relevance of this information to the potential for causing similar effects in humans.
Hazard index: The sum of hazard quotients across multiple chemicals and/or multiple exposure routes.
Hazard quotient: The ratio of a measured or estimated dose to a chemical-specific reference dose through a specific route of exposure.
Hazardous and noxious substance (HNS): Is defined as a substance other than oil which if introduced into the marine environment is likely to create hazards to human health, to harm living resources and marine life, to damage amenities or to interfere with other legitimate uses of the sea.
Hydrolisys: A process by which chemicals reacts with water resulting in its decomposition.
Hypersensibility: The state in which an individual reacts following exposure to a substance (an allergen) with allergic effects after having been previously exposed (sensitised).
IARC: The International Agency for Research on Cancer.
Imposex: A condition caused by low concentrations of organotin compounds (e.g., tributyltins and triphenyltins) characterized by the superimposing of male sex organs on otherwise normal dioecious female gastropods. The resulting pseudohermaphrodites are incapable of reproduction.
In vitro tests: Literally, these are tests conducted outside of the body of the organism in an artificially maintained environment, as in a test tube, culture dish, or bottle. In toxicity testing, they would include studies using isolated enzymes, subcellular organelles, or cultured cells.
In vivo tests: Tests carried out on the intact organism (i.e. within the whole living body), although the evaluation of the toxic endpoint almost always requires pathological or biochemical examination of the test organism's tissues.
Incidence: The number of new cases of a disease within a specified time period. It is frequently presented as the number of new cases per 1,000, 10,000 or 100,000. The incidence rate is a direct estimate of the probability or risk of developing a disease during a specified time period.
Individual: The basic level of ecological organization. For example, a single bird, plant, fish, human, etc.
Induction: The process of causing a quantitative increase in an enzyme as a result of de novo protein synthesis following exposure to an inducing agent. This can occur either by a decrease in the degradation rate or an increase in the synthesis rate or both. Increasing the synthesis rate is the most common mechanism for induction by xenobiotics. Coordinate (pleiotypic) induction is the induction of multiple enzymes by a single-inducing agent. For example, phenobarbital can induce isoforms of both cytochrome P450 and glutathione S-transferase.
Inhalation route: The movement of a chemical from the breathing zone, through the air passageways of the lung, into the alveolar area, across the epithelial cell layer of the alveoli and the endothelial cell layer of the capillary wall and into the blood system.
Inhibition: In its most general sense, inhibition means a restraining or a holding back. In biochemistry and biochemical toxicology, inhibition is a reduction in the rate of an enzymatic reaction, and an inhibitor is any compound causing such a reduction. Inhibition of enzymes important in normal metabolism is a significant mechanism of toxic action of xenobiotics, whereas inhibition of xenobiotic-metabolizing enzymes can have important consequences in the ultimate toxicity of their substrates. Inhibition is sometimes used in toxicology in a more general and rather ill-defined way to refer to the reduction of an overall process of toxicity, as in the inhibition of carcinogenesis by a particular chemical.
Intake: The process by which a substance crosses the outer boundary of an organism without passing an absorption barrier (e.g., through ingestion or inhalation).
Intrinsic properties: Inherent to the individual, chemical, etc.
Irritant: A chemical causing a localised inflammatory reaction to skin or mucous membranes at the site of contact.
IUPAC: International Union of Pure and Applied Chemistry. Among other things, is the responsible for setting rules on chemical nomenclature.
LC50 (median lethal concentration): The concentration of a test chemical that, when a population of test organisms is exposed to it, is estimated to be fatal to 50% of the organisms under the stated conditions of the test. Normally used in lieu of the LD50 test in aquatic toxicology and inhalation toxicology. The LC50 is expressed in terms of weight of test substance per unit volume (mg/L).
LD50 (median lethal dose): The quantity of a chemical compound that, when applied directly to test organisms, is estimated to be fatal to 50% of those organisms under the stated conditions of the test. The LD50 value is the standard for comparison of acute toxicity between toxicants and between species. Because the results of LD50 determinations may vary widely, it is important that both biological and physical conditions be narrowly defined (e.g., strain, gender, and age of test organism; time and route of exposure; environmental conditions). The value may be determined graphically from a plot of log dose against mortality expressed in probability units (probits) or, more recently, by using one of several computer programs available. The LD50 is expressed in terms of weight of test substance per unit weight of test animal (mg/kg).
Leaching: It is the movement of a chemical from soil or sediment to water (surface or groundwater).
Lethality: Death.
Linear model: A model in which the change in a biological effect is proportional to the change in dose or duration of exposure.
Lipophilic: (1) Fat-loving; the degree to which a chemical partitions into fat versus water. (2) The physical property of chemical compounds that causes them to be soluble in nonpolar solvents (e.g., chloroform and benzene) and, generally, relatively insoluble in polar solvents such as water. This property is important toxicologically because lipophilic compounds tend to enter the body easily and to be excretable only when they have been rendered less lipophilic by metabolic action.
Measure of effect: Quantitative estimates or measurements of toxicity used in an ecological risk assessment to properly evaluate management goals and assessment endpoints.
Mechanism of action / Mode of action (mode of toxic action): Terms used to describe the mechanism(s) that enables a toxicant to exert its toxic effect. The term(s) may be narrowly used to describe only those events at the site of action (perhaps better referred to as mechanism of action) or more broadly, to describe the sequence of events from uptake from the environment, through metabolism, distribution, and so on, up to and including events at the site of action.
Metabolism: The biochemical reactions that take place within an organism. It involves two processes: anabolism (assimilation or constructive processes) and catabolism (disintegration or destructive processes). All metabolic processes involve energy transfer.
Metals: A grouping of elements generally characterized by opacity, ductility, luster, being electropositive with a tendency to lose electrons, and having the property of conducting heat and electricity. Heavy metals may be further defined as any element having a density greater than 5 g/cm3, and those of toxicological significance preferentially bind to ligands containing sulphur or nitrogen (arsenic, cadmium, chromium, lead, and mercury).
Microarray: Microarrays are based on the principle that any gene being expressed at any point in time is giving rise to a specific, corresponding mRNA. The microarray itself consists of spots of DNA (c. 200 μ) bound to a suitable matrix. The mRNAs in the biological sample in question bind to the corresponding DNA and can be visualized by techniques involving dyes. Given the complexity of the data obtained (often thousands of genes are evaluated on a single microarray), special techniques have been developed for array scanning, data extraction, and statistical analysis.
Mixed Function Oxidase (MFO): An important group of Phase I enzymes that metabolize a wide variety of chemicals. See also Cytochrome P450.
Model: A mathematical representation of a natural system intended to mimic the behaviour of the real system, allowing description of empirical data, and predictions about untested states of the system.
Monooxygenase (mixed-function oxidase): An enzyme for which the cosubstrates are an organic compound and molecular oxygen. In reactions catalyzed by these enzymes, one atom of a molecule of oxygen is incorporated into the substrate whereas the other atom is reduced to water. Monooxygenases of importance in toxicology include cytochrome P450 and the flavin-containing monooxygenase, both of which initiate the metabolism of lipophilic xenobiotics by the introduction of a reactive polar group into the molecule. Such reactions may represent detoxication or may generate reactive intermediates of importance in toxic action. The term mixed-function oxidase is now considered obsolete and should not be used. The term multifunction oxidase was never widely adopted and also should not be used.
MSDS: Material Safety Data Sheet. Also known as Safety Data Sheet.
Mutagenesis: It is the ability of chemicals to cause changes in the genetic material in the nucleus of cells in ways that allow the changes to be transmitted during cell division.
Mutagens: Chemicals capable of causing mutations (heritable changes produced in the genetic information stored in the DNA of living cells).
Neurotoxicity or neurotoxic effect: It is defined as an adverse change in the chemistry, structure, or function of the nervous system following exposure to a chemical or physical agent.
Neurotoxin: A chemical that causes an adverse effect on the nervous system.
Non-genotoxic carcinogens: Chemical carcinogenics that cause cancer by effects other than direct damage to the genetic material.
No Observed Effect Concentration (NOEC): The highest concentration of toxicant to which organisms are exposed in a full or partial life-cycle (short-term) test, that causes no observable adverse effects on the test organisms (i.e., the highest concentration of toxicant in which the values for the observed responses are not statistically significantly different from the controls). This value is used, along with other factors, to determine toxicity limits in permits.
No Observed Effect Level (NOEL): This is the highest dose level of a chemical that, in a given toxicity test, causes no observable effect in the test animals. The NOEL for a given chemical varies with the route and duration of exposure and the nature of the adverse effect (i.e., the indicator of toxicity). The NOEL for the most sensitive test species and the most sensitive indicator of toxicity is usually employed for regulatory purposes. Effects considered are usually adverse effects, and this value may be called the No Observed Adverse Effects level (NOAEL).
No-threshold dose-response relationship: A dose-response relationship that assumes that any dose carries some probability of an effect.
Octanol-water partition coefficient (Kow, P): The ratio of the concentrations of a chemical in the water phase and the n-octanol phase after the chemical is equilibrated between equal volumes of the two solvents.
OECD: Organisation for Economic Co-operation and Development.
Oral route: The entry of a chemical into the body by way of the gastrointestinal tract. Although absorption to some extent takes place throughout the tract, the majority of the absorption takes place in the area of the villi of the small intestine.
Organic chemistry: It is the branch of chemistry dealing with compounds containing carbon-carbon bonds. These carbon compounds are highly volatile. Chemicals studied in organic chemistry include hydrocarbons, compounds containing only carbon and hydrogen, as well as myriad compositions based always on carbon, but also containing other elements like hydrogen, nitrogen, oxygen, phosphorus, sulphur, etc.
Organochlorine pesticides: These compounds are extremely stable and persistent in the environment and can accumulate in food chains. They are efficiently absorbed by ingestion and act on the central nervous system to stimulate or depress it. Signs and symptoms of toxicity vary with the specific chemical. In general, mild poisoning cases cause symptoms such as dizziness, nausea, abdominal pain, and vomiting. In chronic poisoning, weight loss and loss of appetite, temporary deafness and disorientation can occur.
Organophosphate pesticides: These are irreversible inhibitors of cholinesterase, thus allowing accumulating of acetylcholine at nerve endings. They are rapidly absorbed into the body by ingestion, through intact skin, including the eye and by inhalation. Poisoning symptoms range from headache, fatigue, dizziness, vomiting and cramps in mild cases, to the rapid onset of unconsciousness, local or generalized seizure and other manifestations of a cholinergic crisis in severe cases.
Oxidative stress: Damage to cells and cellular constituents and processes by reactive oxygen species generated in situ. Oxidative stress may be involved in such toxic interactions as DNA damage, lipid peroxidation and pulmonary and cardiac toxicity. Because of the transitory nature of most reactive oxygen species, although oxidative stress is often invoked as a mechanism of toxicity, rigorous proof may be lacking. See also Reactive oxygen species.
Ozone: A gas that is a form of oxygen. Ozone can be beneficial if it is high in the atmosphere because it protects us from the harmful rays of the sun (stratospheric ozone). Ozone is harmful when it is close to the ground because it is a major air pollutant that can cause respiratory illnesses (Tropospheric ozone).
PAHs (Polynuclear aromatic hydrocarbons): Naturally occurring chemicals formed as a result of incomplete combustion. Several of the chemicals in this group are carcinogenic.
Paracelsus: The founder of modern toxicology.
Partition coefficient: This is a measure of the relative lipid solubility of a chemical and is determined by measuring the partitioning of the compound between an organic phase and an aqueous phase (e.g., octanol and water). The partition coefficient is important in studies of the uptake of toxicants because compounds with high coefficients (lipophilic compounds) are usually taken up more readily by organisms and tissues.
PCBs (Polychlorinated biphenyls): A manufactured group of chemicals used for their insulating properties. Several of the chemicals in this group are carcinogenic.
Personal protective equipment: Any devices worn by individuals as protection against hazards in the environment or the workplace, including respirators, gloves, goggles and earmuffs.
Pesticide: Any substance used to destroy or inhibit the action of plant or animal pests. See also Organochlorine pesticides and Organophosphate pesticides.
Pharmacokinetics: The study of the quantitative relationship between absorption, distribution, and excretion of chemicals and their metabolites. It involves derivation of rate constants for each of these processes and their integration into mathematical models that can predict the distribution of the chemical throughout the body compartments at any point in time after administration. Pharmacokinetic studies have been carried out most extensively in the case of clinical drugs. When applied specifically to toxicants, the term toxicokinetics is often used.
Phase I (metabolism): The first step in drug metabolism. Its purpose is to aid the elimination of foreign compounds from the body. The main reactions involved are oxidation, reduction, and hydrolysis but could also be hydration or isomerization. The aim of phase I is to add or unmask a reactive functional group to which phase II metabolic enzymes can add a highly water-soluble molecule. This is desired because the more water soluble a compound, the more readily it is excreted by the kidneys. Although some compounds can be eliminated solely as a result of phase I drug metabolism, most go on to be involved in the conjugation reactions of phase II metabolism. Also, phase I is not a necessary precursor to phase II metabolism for some foreign molecules. The products of Phase I reactions may be potent electrophiles that can be conjugated and detoxified in Phase II reactions or that may react with nucleophilic groups on cellular constituents, thereby causing toxicity.
Phase II reactions: Reactions involving the conjugation with endogenous substrates of Phase I products and other xenobiotics that contain functional groups such as hydroxyl, amino, carboxyl, epoxide, or halogen. The endogenous metabolites include sugars, amino acids, glutathione, and sulfate. The conjugation products, with rare exceptions, are more polar, less toxic, and more readily excreted than are their parent compounds. There are two general types of conjugations: type I (e.g., glycoside and sulfate formation), in which an activated conjugating agent combines with substrate to yield the conjugated product; and type II (e.g., amino acid conjugation), in which the substrate is activated and then combines with an amino acid to yield a conjugated product.
Poison (toxicant): It is any substance that causes a harmful effect when administered to a living organism. Due to a popular connotation that poisons are, by definition, fatal in their effects and that their administration is usually involved with attempted homicide or suicide, most toxicologists prefer the less prejudicial term toxicant. Poison is a quantitative concept. Almost any substance is harmful at some dose and, at the same time, is harmless at a very low dose. There is a range of possible effects, from subtle long-term chronic toxicity to immediate lethality.
Pollution: This is contamination of soil, water, food or the atmosphere by the discharge or admixture of noxious materials. A pollutant is any chemical or substance contaminating the environment and contributing to pollution.
Population: Comprises groups of individuals of the same species existing within a defined geographical location. For example, populations of humans, daffodils, chestnut trees, etc.
Potency: The relative degree of toxic effects caused by a chemical at a specific dose.
Precautionary principle: In situations when an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some cause-and-effect relationships are not fully established scientifically.
Preparation: An international physical mixture of two or more substances between which no chemical reaction takes place.
Primary irritant: A chemical that causes an inflammatory reaction on first contact.
Probabilistic assessment: A risk assessment involving the use of distributions of exposure parameters and resulting in a distribution of possible risks; incorporates variability into a risk assessment.
Problem formulation: The initial stage of an ecological risk assessment where the problem is defined and the scope and endpoints of the assessment are identified.
REACH (Registration, Evaluation and Authorization of Chemicals): This is a far-reaching European legislation replacing all previous patchy EU toxic substances control legislations. REACH aims to comprehensively regulate the manufacture, import and commerce of hazardous substances and their preparations in the European Union.
Reactive intermediates (reactive metabolites): Chemical compounds, produced during the metabolism of xenobiotics that are more chemically reactive than is the parent compound. Although they are susceptible to detoxication by conjugation reactions, these metabolites, as a consequence of their increased reactivity, have a greater potential for adverse effects than does the parent compound. A well-known example is the metabolism of benzo(a)pyrene to its carcinogenic dihydrodiol epoxide derivative as a result of metabolism by cytochrome P450 and epoxide hydrolase. Reactive intermediates involved in toxic effects include epoxides, quinones, free radicals, reactive oxygen species, and a small number of unstable conjugation products.
Reactive oxygen species: Molecular oxygen normally exists in a relatively unreactive triplet state (3O2). However, reactive species such as superoxide anion, hydrogen peroxide, singlet oxygen, and the highly reactive hydroxyl radical are also known. Reactive oxygen species are formed in vivo, either during, or as a consequence of, aerobic metabolism. There is a great deal of evidence that these reactive oxygen species are linked to a number of toxic endpoints, and this phenomenon is known as oxidative stress.
Receptor: A risk assessment term describing a hypothetical individual or group of organisms assumed to be exposed to a chemical.
Redistribution: The transfer of a chemical from one tissue or organ to another over time (e.g., liver to bone).
Reference Dose (RfD): See Acceptable Daily Intake (ADI).
Reproductive toxicology: Is the study of the occurrence of adverse effects on the male or female reproductive system that may result from exposure to chemical or physical agents.
Resistance: See adaptation to toxicants.
Risk, toxicologic: The probability that some adverse effect will result from a given exposure to a chemical is known as the risk. It is the estimated frequency of occurrence of an event in a population and may be expressed in absolute terms (e.g., 1 in 1 million) or in terms of relative risk (i.e., the ratio of the risk in question to that in an equivalent unexposed population).
Risk analysis: This term includes risk assessment together with consideration of risk communication and risk management.
Risk assessment: A methodologic approach in which the toxicities of a chemical are identified, characterized and analyzed for dose-response relationships; a mathematical model is applied to the data to generate a numerical estimate that can serve as a guide to allowable exposures. It includes the development of both qualitative and quantitative expression of risk. The process of human health risk assessment may be divided into four major components: hazard identification, dose-response assessment (high-dose to low-dose extrapolation), exposure assessment and risk characterization.
Risk characterization: A component of risk assessment that describes the nature and magnitude of risk, including uncertainty. In human health risk assessment, it includes the summary and interpretation of information gathered from previous steps (e.g., data evaluation, dose-response assessment, exposure assessment), including the results of a probabilistic analysis.
Risk communication: The process of making risk assessment and risk management information understandable to the layperson.
Risk description: A portion of the risk characterization, component of an ecological risk assessment, in which the significance of any estimated adverse effects is interpreted from the lines of evidence used to estimate risk.
Risk estimation: A portion of the risk characterization, component of an ecological risk assessment, in which exposure and effects data are compared. This is parallel to the risk characterization component of a human health risk assessment.
Risk management: The process of applying a risk assessment to the conditions that exist in society, so as to balance exposures to toxic agents against needs for products and processes that may be inherently hazardous.
Route of exposure: Portal of entry of a chemical into the body: oral, inhalation, dermal, or injection.
Sensitisation: The immune process by which individuals become hypersensitive to a substance to which they are exposed. Subsequent exposures can lead to the development of an allergy.
Soil sorption constant (Koc): The extent of partitioning of an organic chemical between the solid and solution phases of a water-saturated soil or sediment.
Solvents: In toxicology, this term usually refers to industrial solvents. These belong to many different chemical classes, and a number of these are known to cause problems of toxicity to humans. They include aliphatic hydrocarbons (e.g., hexane), halogenated aliphatic hydrogens (e.g., methylene chloride), aliphatic alcohols (e.g., methanol), glycols and glycol ethers (e.g., propylene and propylene glycol), and aromatic hydrocarbons (e.g., toluene).
Sorption: It's defined as both adsorption and absorption occurring simultaneously.
Subchronic: Characterized by a time period of intermediate duration; commonly used to describe exposure between acute and chronic durations in toxicity studies (usually 3 months).
Subchronic toxicity: Toxicity due to chronic exposure to quantities of a toxicant that do not cause any evident acute toxicity for a time period that is extended but is not so long as to constitute a significant part of the life span of the species in question. In subchronic toxicity tests using mammals, a 30-90 day period is considered appropriate.
Subchronic toxicity study: Multiple-dose study in which animals are treated for less than 6 months. They are intended to elucidate the target organs for toxicity and demonstrate dose-response relationships.
Substance: Chemical elements and their compounds as they occur in the natural state or as produced by industry, including any additives required for the purpose of placing them on the market (EINECS).
Target organ effects: Chemically induced adverse effects on specific organs or systems in the body. For example, toluene is a hepatotoxin (causes adverse effects on the liver).
Teratogenesis: This term refers to the production of defects in the reproduction process resulting in either reduced productivity due to fetal or embryonic mortality or the birth of offspring with physical, mental, behavioral, or developmental defects. Compounds causing such defects are known as teratogens.
Threshold dose: The dose of a toxicant below which no adverse effect occurs. The existence of such a threshold is based on the fundamental tenet of toxicology that, for any chemical, there exists a range of doses over which the severity of the observed effect is directly related to the dose, the threshold level representing the lower limit of this dose range. Although practical thresholds are considered to exist for most adverse effects, for regulatory purposes it is assumed that there is no threshold dose for carcinogens.
Threshold dose-response relationship: A dose-response relationship that assumes that adverse effects occur only when a threshold dose is exceeded.
Tolerance: See adaptation to toxicants.
Toxic substances control act (TSCA): US law governing dangerous (hazardous) substances (equivalent to EINECS), effective from 1 January 1977. Controls the exposure to and use of raw industrial chemicals not subjec to other laws. New chemicals are to be evaluated prior to manufacture and can be controled based on the risk.
Toxic agent: Chemical or physical agents that, under certain circumstances of exposure, can cause harmful effects to living organisms.
Toxicant: It is used when speaking of toxic substances that are produced by or are a by-product of anthropogenic (human-made) activities. Some toxicants can be produced by both natural and anthropogenic activities. A toxicant is an agent that can result in the occurrence of a structural or functional adverse effect in a biological system. See also Poison.
Toxicity: The intrinsic degree to which a chemical causes adverse effects.
Toxicodynamics: Describes the time-course of toxic action at the target site, subsequent physiological impairment of the organism as well as the influence of any compensating mechanisms (i.e., any damage recovery) and finally the emergence of toxic effects at the level of the organism such as mortality. Thus, the toxicodynamics describes the mechanism of action and potency of the chemical at the site of action i.e. what the toxicant does to the organism.
Toxicogenomics: Those aspects of genomics of relevance to toxicology (see genomics).
Toxicokinetics: The process of the uptake of potentially toxic substances by the body, the biotransformations they undergo, the distribution of the substances and their metabolites in the tissues and the elimination of the substances and their metabolites from the body. Both the amounts and the concentration of the substances as well as their metabolites are studied. The term has essentially the same meaning as Pharmacokinetics, but the latter term is usually restricted to the study of pharmaceutical substances.
Toxicology: Toxicology is defined as that branch of science that deals with poisons (toxicants) and their effects. It is the study of the adverse effects of biological, chemical or physical agents on living organisms and the ecosystems, including the prevention and amelioration of such adverse effects. A poison is defined as any substance that causes a harmful effect when administered, either by accident or design, to a living organism, as mentioned above. There are difficulties in bringing a more precise definition to the meaning of poison and in the definition and measurement of toxic effect. The range of deleterious effects is wide and varies with species, gender, and developmental stage and so on, while the effects of toxicants are always dose dependent.
Toxin: The term toxin generally refers to toxic substances that are produced by biological systems such as plants, animals, fungi, or bacteria. In other words, it is a toxicant produced by a living organism. Toxin should never be used as a synonym for toxicant.
Transport: In toxicology, this term refers to the mechanisms that bring about movement of toxicants and their metabolites from one site in the organism to another. Usually involves binding to either blood albumins or blood lipoproteins.
Transport medium: A medium (i.e., water, air, or soil) through which chemicals can move to locations remote from their source.
Vapour: Is defined as the gaseous component of a solid or liquid material below the critical temperature.
Venom: A venom is a toxin produced by an animal specifically for the poisoning of other species via a mechanism designed to deliver the toxin to its prey. Examples include the venom of bees and wasps, delivered by a sting, and the venom of snakes, delivered by fangs.
Volatilization: Upward movement of chemicals in the vapour phase from soil or water into air.
Water pollution: Water pollution is of concern in both industrialized and nonindustrialized nations. Chemical contamination is more common in industrialized nations, whereas microbial contamination is more important in nonindustrialized areas. Surface water contamination has been the primary cause for concern but, since the discovery of agricultural and industrial chemicals in groundwater, contamination of water from this source is also a problem. Water pollution may arise from runoff of agricultural chemicals, from sewage or from specific industrial sources. Agricultural chemicals found in water include insecticides, herbicides, fungicides, and nematocides; fertilizers, although less of a toxic hazard, contribute to such environmental problems as eutrophication. Other chemicals of concern include low molecular-weight halogenated hydrocarbons such as chloroform, dichloroethane, and carbon tetrachloride; polychlorinated biphenyls (PCBs); chlorophenols; 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); phthalate ester plasticizers; detergents; and a number of toxic inorganics.
Xenobiotic: (1) A general term used to describe any chemical interacting with an organism that does not occur in the normal metabolic pathways of that organism. The use of this term in lieu of "foreign compound" among others, has gained wide acceptance. (2) A substance not normally present in the environment, such as a pesticide or pollutant.
FINAL NOTE: More key terms can be found in the following glossary:
http://sis.nlm.nih.gov/enviro/iupacglossary/frontmatter.html