a priori: The formulation of a hypothesis before undertaking an investigation or experiment.
Acceptable Daily Intake (ADI): Estimate of the amount of a substance in food or drink, expressed on a body weight basis (e.g. mg/kg bodyweight), that can be ingested daily over a lifetime by humans without appreciable health risk.
Acute: Short term, in relation to exposure or effect.
Acute reference dose (ARfD): Estimate of the amount of a substance in food or drink, expressed on a body weight basis, that can be ingested in a period of 24 hours or less without appreciable health risk.
Acute toxicity: Effects that occur over a short period of time (up to 14 days) immediately following exposure.
Adduct: A chemical grouping which is covalently bound (see covalent binding) to a large molecule such as DNA (qv) or protein.
Adenoma: A benign neoplasm arising from a gland forming epithelial tissue such as colon, stomach or respiratory tract.
Adverse effect: Change in morphology, physiology, biochemistry, growth, development or lifespan of an organism which results in impairment of functional capacity or impairment of capacity to compensate for additional stress or increase in susceptibility to the harmful effects of other environmental influences.
Ah receptor: The Ah (Aromatic hydrocarbon) receptor protein regulates some specific gene expressions associated with toxicity. The identity of the natural endogenous chemicals which bind to the Ah receptor is unknown. Binding to the Ah receptor is an integral part of the toxicological mechanism of a range of chemicals, such as chlorinated dibenzodioxins and polychlorinated biphenyls.
Alkylating agents: Chemicals which leave an alkyl group covalently bound to biologically important molecules such as proteins and nucleic acids (see adduct). Many alkylating agents are mutagenic, carcinogenic and immunosuppressive.
Allele: Alternative form of a gene.
Allergen: Substance capable of stimulating an allergic reaction.
Allergy: The adverse health effects that may result from the stimulation of a specific immune response.
Allergic reaction: an adverse reaction elicited by exposure to a previously sensitised individual to the relevant antigen.
Ames test: In vitro (qv) assay for bacterial gene mutations (qv) using strains of Salmonella typhimurium developed by Ames and his colleagues.
Androgen: The generic term for any natural or synthetic compound that can interact with and activate the androgen receptor. In mammals, androgens (for example, androstenedione and testosterone) are synthesised by the adrenal glands and the testes and promote development and maintenance of male secondary sexual characteristics.
Aneugenic: Inducing aneuploidy (qv).
Aneuploidy: The circumstances in which the total number of chromosomes within a cell is not an exact multiple of the normal haploid (see 'polyploidy') number. Chromosomes may be lost or gained during cell division.
Apoptosis: A form of active cell death resulting in fragmentation of the cell into membrane-bound fragments (apoptotic bodies). These are usually rapidly removed in vivo by engulfment by phagocytic cells. Apoptosis can occur normally during development, but is often triggered by toxic stimuli.
Base pair (bp): Two complementary nucleotide (qv) bases joined together by chemical bonds.
Benchmark dose (BMD) modelling: An approach to dose-response assessment that aims to be more quantitative than the NOAEL process. This approach constructs mathematical models to fit all data points in the dose-response study and uses the best fitting model to interpolate an estimate of the dose that corresponds to a particular level of response (a benchmark response), often 10%. A measure of uncertainty is also calculated, and the lower confidence limit on the benchmark dose is called the BMDL. The BMDL accounts for the uncertainty in the estimate of the dose-response that is due to characteristics of the experimental design such as sample size. The BMDL can be used as the point of departure for derivation of a health-based guidance value or a margin of exposure.
Bias: In the context of epidemiological studies, an interference which at any stage of an investigation tends to produce results that depart systematically from the true values (to be distinguished from random error). The term does not necessarily carry an imputation of prejudice or any other subjective factor such as the experimenter's desire for a particular outcome.
Bioavailability: A term referring to the proportion of a substance which reaches the systemic circulation unchanged after a particular route of administration.
Bioinformatics: The science of informatics as applied to biological research. Informatics is the management and analysis of data using advanced computing techniques. Bioinformatics is particularly important as an adjunct to genomics research, because of the large amount of complex data this research generates.
Biomarker: Observable change (not necessarily pathological) in an organism, related to a specific exposure or effect.
Body burden: Total amount of a chemical present in an organism at a given time.
Bradford Hill Criteria: Sir Austin Bradford-Hill established criteria that may be used to assist in the interpretation of associations reported from epidemiological studies:
- Strength – The stronger the association the more likely it is causal. The COC has previously noted that the relative risks of <3 need careful assessment for effects of bias or confounding.
- Consistency – The association has been consistently identified by studies using different approaches and is also seen in different populations with exposure to the chemical under consideration.
- Specificity – Limitation of the association to specific exposure groups or to specific types of disease increases likelihood that the association is causal.
- Temporality – The association must demonstrate that exposure leads to disease. The relationship of time since first exposure, duration of exposure and time since last exposure are all important in assessing causality.
- Biological gradient – If an association reveals a biological gradient or dose-response curve, then this evidence is of particular importance in assessing causality.
- Plausibility – Is there appropriate data to suggest a mechanism by which exposure could lead to concern? However, even if an observed association may be new to science or medicine it should not be dismissed.
- Coherence – Cause and effect interpretation of data should not seriously conflict with generally known facts.
- Experiment – Can the association be demonstrated? Evidence from experimental animals may assist in some cases. Evidence that removal of the exposure leads to a decrease in risk may be relevant.
- Analogy – Have other closely related chemicals been associated with the disease?
Bronchial: Relating to the air passages conducting air from the trachea (windpipe) to the lungs.
C. elegans: Caenorhabditis elegans, a nematode or roundworm, the first animal to have its genome completely sequenced and all the genes fully characterised.
Cancer: Synonym for a malignant neoplasm – that is, a tumour (qv) that grows progressively, invades local tissues and spreads to distant sites (see also tumour and metastasis).
Candidate gene: A gene that has been implicated in causing or contributing to the development of a particular disease.
Carcinogenesis: The origin, causation and development of tumours (qv). The term applies to benign as well as malignant neoplasms and not just to carcinomas (qv).
Carcinogenicity bioassay: Tests carried out in laboratory animals, usually rats and mice, to determine whether a substance is carcinogenic. The test material is given throughout life to groups of animals at different dose levels.
Carcinogens: The causal agents which induce tumours. They include external factors (chemicals, physical agents, viruses) and internal factors such as hormones. Chemical carcinogens are structurally diverse and include naturally-occurring substances as well as synthetic compounds. An important distinction can be drawn between genotoxic (qv) carcinogens which have been shown to react with and mutate DNA, and non-genotoxic carcinogens which act through other mechanisms. The activity of genotoxic carcinogens can often be predicted from their chemical structure - either of the parent compound or of active metabolites (qv). Most chemical carcinogens exert their effects after prolonged exposure, show a dose-response relationship and tend to act on a limited range of susceptible target tissues. Carcinogens are sometimes species or sex-specific and the term should be qualified by the appropriate descriptive adjectives to aid clarity. Several different chemical and other carcinogens may interact, and constitutional factors (genetic susceptibility, hormonal status) may also contribute, emphasising the multifactorial nature of the carcinogenic process.
Carcinoma: Malignant tumour arising from epithelial cells lining, for example, the alimentary, respiratory and urogenital tracts and from epidermis, also from solid viscera such as the liver, pancreas, kidneys and some endocrine glands. (See also 'tumour').
Case-control study: (Synonyms - case comparison study, case referent study, retrospective study) A comparison is made of the proportion of cases who have been exposed to a particular hazard (e.g. a carcinogen) with the proportion of controls who have been exposed to the hazard.
Cell transformation: The process by which a normal cell acquires the capacity for neoplastic growth. Complete transformation occurs in several stages both in vitro and in vivo. One step which has been identified in vitro is 'immortalisation' by which a cell acquires the ability to divide indefinitely in culture. Such cells do not have the capacity to form tumours in animals, but can be induced to do so by extended passage in vitro, by treatment with chemicals, or by transfection with oncogene DNA. The transformed phenotype so generated is usually, but not always, associated with the ability of the cells to grow in soft agar and to form tumours when transplanted into animals. It should be noted that each of these stages of transformation can involve multiple events which may or may not be genetic. The order in which these events take place, if they occur at all, in vivo is not known.
Chromosomal aberrations: Collective term of particular types of chromosome damage induced after exposure to exogenous chemical or physical agents which damage the DNA. (see clastogen).
Chromosome: In simple prokaryotic organisms, such as bacteria and most viruses, the chromosome consists of a single circular molecule of DNA containing the entire genetic material of the cell. In eukaryotic cells, the chromosomes are thread-like structures, composed mainly of DNA and protein, which are present within the nuclei of every cell. They occur in pairs, the numbers varying from one to more than 100 per nucleus in different species. Normal somatic cells in humans have 23 pairs of chromosomes, each consisting of linear sequences of DNA which are known as genes (qv).
Chronic effect: Consequence which develops slowly and has a long-lasting course (often but not always irreversible).
Chronic exposure: Continued exposures occurring over an extended period of time, or a significant fraction of the life-time of a human or test animal.
Clastogen: An agent that produces chromosome breaks and other structural aberrations such as translocations. Clastogens may be viruses or physical agents as well as chemicals. Clastogenic events play an important part in the development of some tumours.
Clearance: Volume of blood or plasma, or mass of an organ, effectively cleared of a substance by elimination (metabolism and excretion) in a given time interval. Total clearance is the sum or the clearances for each eliminating organ or tissue.
Clone: A term which is applied to genes, cells, or entire organisms which are derived from - and are genetically identical to - a single common ancestor gene, cell, or organism, respectively. Cloning of genes and cells to create many copies in the laboratory is a common procedure essential for biomedical research.
Coding regions: those parts of the DNA that contain the information needed to form proteins. Other parts of the DNA may have non-coding functions (e.g. start-stop, pointing or timer functions) or as yet unresolved functions or maybe even ‘noise’.
Codon: a set of three nucleotide bases in a DNA or RNA sequence, which together code for a unique amino acid.
Cohort: A defined population that continues to exist through time.
Cohort study: (Synonyms - follow-up, longitudinal study) The study of a group of people defined at a particular point in time (the cohort), who have particular characteristics in common, such as a particular exposure. They are then observed over a period of time for the occurrence of disease. The rate at which the disease develops in the cohort is compared with the rate in a comparison population, in which the characteristics (e.g. exposure) are absent.
Complementary DNA (cDNA): cDNA is DNA that is synthesised in the laboratory from mRNA by reverse transcription. A cDNA is so-called because its sequence is the complement of the original mRNA sequence.
Confounding variable: (synonym - confounder) An extraneous variable that satisfies BOTH of 2 conditions: (1) it is a risk factor for the disease under study (2) it is associated with the study exposure but is not a consequence of exposure. For example cigarette smoking is a confounding variable with respect to an association between alcohol consumption and heart disease. Failure to adjust for a confounding variable results in distortion of the apparent magnitude of the effect of the exposure under study. (In the example, smoking is a risk factor for heart disease and is associated with alcohol consumption but is not a consequence of alcohol consumption.)
Congeners: Related compounds varying in chemical structure but with similar biological properties.
Covalent binding: Chemical bonding formed by the sharing of an electron pair between two atoms. Molecules are combinations of atoms bound together by covalent bonds.
Cytochrome P450 (CYP): An extensive family of haem-containing proteins involved in enzymic oxidation of a wide range of endogenous and xenobiotic (qv) substances and their conversion to forms that may be more easily excreted. In some cases the metabolites produced may be reactive and may have increased toxicity. In other cases the substances may be natural precursors of hormones (e.g. steroids).
Cytogenetic: Concerning chromosomes, their origin, structure and function.
Deletion: A chromosomal aberration in which a proportion of the chromosome is lost. Deletions may range in size from a single nucleotide (qv) to an entire chromosome. Such deletions may be harmless, may result in disease, or may in rare cases be beneficial.
DNA (Deoxyribonucleic Acid): The carrier of genetic information for all living organisms except the group of RNA viruses. Each of the 46 chromosomes in normal human cells consists of 2 strands of DNA containing up to 100,000 nucleotides, specific sequences of which make up genes (qv). DNA itself is composed of two interwound chains of linked nucleotides (qv).
DNA probe: A piece of single-stranded DNA, typically labelled so that it can be detected (for example, a radioactive or fluorescent label can be used), which can single out and bind with (and only with) another specific piece of DNA. DNA probes can be used to determine which sequences are present in a given length of DNA or which genes are present in a sample of DNA.
DNA repair genes: Genes which code for proteins that correct damage in DNA sequences. When these genes are altered, mutations may be able to accumulate in the genome, ultimately resulting in disease.
Dominant lethal assay: See Dominant Lethal mutation.
Dominant lethal mutation: A dominant mutation that causes death of an early embryo.
Dose: Total amount of a substance administered to, taken or absorbed by an organism.
Endocrine modulator (synonym – endocrine disruptor): A chemical, which can be naturally occurring or man-made, that causes adverse health effects in an organism, as a result of changes in hormonal function.
Endonuclease: An enzyme that cleaves its nucleic acid substrate at internal sites in the nucleotide sequence.
Enterohepatic circulation: Cyclical process involving intestinal re-absorption of a substance that has been excreted through bile followed by transfer back to the liver, making it available for biliary excretion again.
Epidemiology: Study of the distribution and the aetiology of disease in humans.
Epithelium: The tissue covering the outer surface of the body, the mucous membranes and cavities of the body.
Erythema: Reddening of the skin due to congestion of blood or increased blood flow in the skin.
Erythrocyte: Red blood cell.
Estrogen: Sex hormone or other substance capable of developing and maintaining female characteristics of the body.
Exogenous: Arising outside the body.
Fibrosarcoma: A malignant tumour arising from connective tissue (see 'tumour').
Fluorescence In-Situ Hybridisation: A technique which allows individual chromosomes and their centromeres to be visualised in cells.
Fetotoxic: Causing toxic, potentially lethal effects to the developing fetus.
Forestomach: (See glandular stomach).
Full gene sequence: the complete order of bases in a gene. This order determines which protein a gene will produce.
Gavage: Administration of a liquid via a stomach tube, commonly used as a dosing method in toxicity studies.
Gene: The functional unit of inheritance: a specific sequence of nucleotides along the DNA molecule, forming part of a chromosome (qv).
Gene expression: The process by which the information in a gene is used to create proteins or polypeptides.
Gene families: Groups of closely related genes that make similar products.
Gene product: The protein or polypeptide coded for by a gene.
Genetic engineering: Altering the genetic material of cells or organisms in order to make them capable of making new substances or performing new functions.
Genetic polymorphism: a difference in DNA sequence among individuals, groups, or populations (e.g. a genetic polymorphism might give rise to blue eyes versus brown eyes, or straight hair versus curly hair). Genetic polymorphisms may be the result of chance processes, or may have been induced by external agents (such as viruses or radiation). Changes in DNA sequence which have been confirmed to be caused by external agents are generally called “mutations” rather than “polymorphisms”.
Genetic predisposition: susceptibility to a disease which is related to a polymorphism, which may or may not result in actual development of the disease.
Genetically modified organism (GMO): An organism which has had genetic material inserted into, or removed from, its cells.
Genome: All the genetic material in the chromosomes of a particular organism; its size is generally given as its total number of base pairs.
Genomic DNA: The basic chromosome set consisting of a species-specific number of linkage groups and the genes contained therein.
Genomics: The study of genes and their function.
Genotoxic: The ability of a substance to cause DNA damage, either directly or after metabolic activation (see also carcinogens).
Genotype: The particular genetic pattern seen in the DNA of an individual. 'Genotype' is usually used to refer to the particular pair of alleles that an individual possesses at a certain location in the genome. Compare this with phenotype.
Glandular stomach: The stomach in rodents consists of two separate regions - the forestomach and the glandular stomach. Only the glandular stomach is directly comparable to the human stomach.
Half-life: Time in which the concentration of a substance will be reduced by half, assuming a first order elimination process.
Hazard: Set of inherent properties of a substance, mixture of substances or a process involving substances that make it capable of causing adverse effects to organisms or the environment.
Hepatic: Pertaining to the liver.
Hepatocyte: The principal cell type in the liver, possessing many metabolising enzymes (see 'metabolic activation').
Hepatotoxic: Causing toxicity to the liver.
Horizon Scanning: The systematic examination of potential threats, opportunities
and likely future developments, which are at the margins of current thinking and planning. Horizon scanning may explore novel and unexpected issues, as well as persistent problems and trends. Overall, horizon scanning is intended to improve
the robustness of policies and the evidence base
Human Genome Project: An international research effort aimed at discovering the full sequence of bases in the human genome, led in the UK by the Wellcome Trust and Medical Research Council.
Hyperplasia: An increase in the size of an organ or tissue due to an increase in the number of cells.
Hypertrophy: An increase in the size of an organ or tissue due to an increase in the volume of individual cells within it.
Idiosyncrasy: Specific (and usually unexplained) reaction of an individual to e.g. a chemical exposure to which most other individuals do not react at all. General allergic reactions do not fall into this category.
In situ hybridisation (ISH): Use of a DNA or RNA probe to detect the presence of the complementary DNA sequence in cloned bacterial or cultured eukaryotic cells.
In vitro: A Latin term used to describe effects in biological material outside the living animal (literally 'in glass').
In vivo: A Latin term used to describe effects in living animals (literally 'in life').
Incidence: Number of new cases of illness occurring during a given period in a specific population.
Inducing agent: A chemical which, when administered to an animal, causes an increase in the expression of a particular enzyme. For example, chlorinated dibenzodioxins are inducing agents which act via the Ah-receptor (qv) to induce cytochrome P450 (qv) CYP1A1.
Intraperitoneal: Within the abdominal cavity.
Isomer: Isomers are two or more chemical compounds with the same molecular formula but having different properties owing to a different arrangement of atoms within the molecule. The ß-isomer of alitame is formed when the compound degrades and the atoms within the molecule are rearranged.
kilobase (kb): A length of DNA equal to 1000 nucleotides.
Knockout animals: Genetically engineered animals in which one or more genes, usually present and active in the normal animal, are absent or inactive.
LD50: The dose of a toxic compound that causes death in 50% of a group of experimental animals to which it is administered. It can be used to assess the acute toxicity of a compound, but is being superseded by more refined methods.
Leukaemia: A group of neoplastic disorders (see tumour) affecting blood-forming elements in the bone marrow, characterised by uncontrolled proliferation and disordered differentiation or maturation. Examples include the lymphocytic leukaemia’s which develop from lymphoid cells and the myeloid leukaemia’s which are derived from myeloid cells (producing red blood cells, mainly in bone marrow).
Ligand: A molecule which binds to a receptor.
Lipids: Fats, substances containing a fatty acid and soluble in alcohols or ether, but insoluble in water.
Lipophilic: 'Lipid liking' - a substance which has a tendency to partition into fatty materials.
Lymphocyte: A type of white blood cell that plays central roles in adaptive immune responses.
Lymphoma: Malignant tumours arising from lymphoid tissues. They are usually multifocal, involving lymph nodes, spleen, thymus and sometimes bone marrow, and other sites outside the anatomically defined lymphoid system. (See also 'tumour').
Malignancy: See 'tumour'.
Margin of exposure (MOE) approach: A methodology that allows the comparison of the risks posed by different genotoxic and carcinogenic substances. The MOE approach uses a reference point, often taken from an animal study and corresponding to a dose that causes a low but measurable response in animals. This reference point is then compared with various dietary intake estimates in humans, taking into account differences in consumption patterns.
Messenger RNA (mRNA): The DNA of a gene is transcribed (see transcription) into mRNA molecules, which then serve as a template for the synthesis of proteins.
Meta-analysis: In the context of epidemiology, a statistical analysis of the results from independent studies, which aims to produce a single estimate of an effect.
Metabolic activation: Metabolism of a compound leading to an increase in its activity, whether beneficial (e.g. activation of a pro-drug) or deleterious (e.g. activation to a toxic metabolite).
Metabolic activation system: A cell-free preparation (e.g. from the livers of rats pre-treated with an inducing agent (qv)) added to in vitro tests to mimic the metabolic activation typical of mammals.
Metabolism: Chemical modification of a compound by enzymes within the body, for example by reactions such as hydroxylation (see cytochrome P450), epoxidation or conjugation. Metabolism may result in activation, inactivation, accumulation or excretion of the compound.
Metabolite: Product formed by metabolism of a compound.
Metabonomics: Techniques available to identify the presence and concentrations of metabolites in a biological sample.
Metaphase: Stage of cell division (mitosis and meiosis) during which the chromosomes are arranged on the equator of the nuclear spindle (the collection of microtubule filaments which are responsible for the movement of chromosomes during cell division). As the chromosomes are most easily examined in metaphase, cells are arrested at this stage for microscopical examination for chromosomal aberrations (qv) - known as metaphase analysis.
Metastasis: The process whereby malignant cells become detached from the primary tumour mass, disseminate (mainly in the blood stream or in lymph vessels) and 'seed out' in distant sites where they form secondary or metastatic tumours. Such tumours tend to develop at specific sites and their anatomical distribution is often characteristic; it is non-random.
Micronuclei: Isolated or broken chromosome fragments which are not expelled when the nucleus is lost during cell division, but remain in the body of the cell forming micronuclei. Centromere positive micronuclei contain DNA and/or protein material derived from the centromere. The presence of centromere positive micronuclei following exposure to chemicals can be used to evaluate the aneugenic (qv) potential of chemicals.
Micronucleus test: See Micronuclei.
Mitogen: A stimulus which provokes cell division in somatic cells.
Mitosis: The type of cell division which occurs in somatic cells when they proliferate. Each daughter cell has the same complement of chromosomes as the parent cell.
Mouse lymphoma assay: An in vitro assay for gene mutation in mammalian cells using a mouse lymphoma cell line L5178Y, which is heterozygous for the gene (carries only one functional gene rather than a pair) for the enzyme thymidine kinase (TK+/-). Mutation of that single gene is measured by resistance to toxic trifluorothymidine. Mutant cells produce two forms of colony - large, which represent mutations within the gene and small, which represent large genetic changes in the chromosome such as chromosome aberrations. Thus this assay can provide additional information about the type of mutation which has occurred if colony size is scored.
Mouse spot test: An in vivo test for mutation, in which pregnant mice are dosed with the test compound and mutations are detected by changes (spots) in coat colour of the offspring. Mutations in the melanocytes (skin pigment cells) of the developing fetus are measured.
Mucosal: Regarding the mucosa or mucous membranes, consisting of epithelium (qv) containing glands secreting mucus, with underlying layers of connective tissue and muscle.
Murine: Often taken to mean 'of the mouse', but strictly speaking means of the Family Muridae which includes rats and squirrels.
Mutation: A permanent change in the amount or structure of the genetic material in an organism or cell, which can result in a change in phenotypic characteristics. The alteration may involve a single gene, a block of genes, or a whole chromosome. Mutations involving single genes may be a consequence of effects on single DNA bases (point mutations) or of large changes, including deletions, within the gene. Changes involving whole chromosomes may be numerical or structural. A mutation in the germ cells of sexually reproducing organisms may be transmitted to the offspring, whereas a mutation that occurs in somatic cells may be transferred only to descendent daughter cells.
Mycotoxin: Toxic compound produced by a fungus.
Neoplasm: See 'tumour'.
Neoplastic: Abnormal cells, the growth of which is more rapid that that of other cells.
Nephrotoxicity: Toxicity to the kidney.
Neurobehavioural: Of behaviour determined by the nervous system.
Neurotoxicity: Toxicity to the nervous system.
No observed adverse effect level (NOAEL): The highest administered dose at which no adverse (qv) effect has been observed.
Non-genotoxic: See 'carcinogens'.
Nucleic acid: One of the family of molecules which includes the DNA and RNA molecules. Nucleic acids were so named because they were originally discovered within the nucleus of cells, but they have since been found to exist outside the nucleus as well.
Nucleotide: the "building block" of nucleic acids, such as the DNA molecule. A nucleotide consists of one of four bases - adenine, guanine, cytosine, or thymine - attached to a phosphate-sugar group. In DNA the sugar group is deoxyribose, while in RNA (a DNA-related molecule which helps to translate genetic information into proteins), the sugar group is ribose, and the base uracil substitutes for thymine. Each group of three nucleotides in a gene is known as a codon. A nucleic acid is a long chain of nucleotides joined together, and therefore is sometimes referred to as a "polynucleotide."
Null allele: inactive form of a gene.
Odds ratio (OR): The odds of disease in an exposed group divided by the odds of disease in an unexposed group.
Oedema: Excessive accumulation of fluid in body tissues.
Oestrogen: (See estrogen)
Oligonucleotide: A molecule made up of a small number of nucleotides, typically fewer than 25.
Oncogene: A gene which is associated with the development of cancer (see proto-oncogene).
Organochlorine: A group of chemical compounds, containing multiple chlorine atoms, that are usually of concern as environmental pollutants. Some organochlorines have been manufactured as pesticides or coolants and others arise as contaminants of manufacturing processes or incineration.
Pharmacokinetics: Description of the fate of drugs in the body, including a mathematical account of their absorption, distribution, metabolism and excretion (see toxicokinetics).
Pharmacogenomics: The science of understanding the correlation between an individual patient's genetic make-up (genotype) and their response to drug treatment. Some drugs work well in some patient populations and not as well in others. Studying the genetic basis of patient response to therapeutics allows drug developers to design therapeutic treatments more effectively.
Phenotype: The observable physical, biochemical and physiological characteristics of a cell, tissue, organ or individual, as determined by its genotype and the environment in which it develops.
Phytoestrogen: Any plant substance or metabolite that induces biological responses in vertebrates and can mimic or modulate the actions of endogenous estrogens usually by binding to estrogen receptors.
Plasmid: A structure composed of DNA that is separate from the cell's genome (qv). In bacteria, plasmids confer a variety of traits and can be exchanged between individuals- even those of different species. Plasmids can be manipulated in the laboratory to deliver specific genetic sequences into a cell.
Plasticiser: A substance which increases the flexibility of certain plastics.
Polymer: A very large molecule comprising a chain of many similar or identical molecular sub units (monomers) joined together (polymerised). An example is the polymer glycogen, formed from linked molecules of the monomer glucose.
Polymerase chain reaction (PCR): A method for creating millions of copies of a particular segment of DNA. PCR can be used to amplify the amount of a particular DNA sequence until there are enough copies available to be detected.
Polymorphism: (see genetic polymorphism)
32P postlabelling: A sensitive experimental method designed to measure low levels of DNA adducts induced by chemical treatment.
Prevalence: The number of cases of a disease that are present in a population at a given time.
Primer: Short pre-existing polynucleotide chain to which new deoxyribonucleotides can be added by DNA polymerase.
Proteomics: The determination of the function of all of the proteins encoded by the organism's entire genome.
Proto-oncogene: One of a group of normal genes which are concerned with the control of cellular proliferation and differentiation. They can be activated in various ways to forms (oncogenes) which are closely associated with one or more steps in carcinogenesis. Activating agents include chemicals and viruses. The process of proto-oncogene activation is thought to play an important part at several stages in the development of tumours.
Receptor: A small, discrete protein in the cell membrane or within the cell with which specific molecules interact to initiate a change in the working of a cell.
Recombinant DNA: DNA molecules that have been created by combining DNA more than one source.
Reference nutrient intake (RNI): An amount of the nutrient that is enough, or more than enough, for most (usually at least 97%) of people in a group. If the average intake of a group is at the RNI, then the risk of deficiency in the group is very small.
Regulatory gene: A gene which controls the protein-synthesising activity of other genes.
Relative risk: A measure of the association between exposure and outcome. The rate of disease in the exposed population divided by the rate of disease among the unexposed population in a cohort study or a population-based case control study. A relative risk of 2 means that the exposed group has twice the disease risk compared to the unexposed group.
Renal: Relating to the kidney.
Reporter gene: A gene that encodes an easily assayed product that is coupled to the upstream sequence of another gene and transfected (qv) into cells. The reporter gene can then be used to see which factors activate response elements in the upstream region of the gene of interest.
Risk: Possibility that a harmful event (death, injury or loss) arising from exposure to a chemical or physical agent may occur under specific conditions.
RNA (ribonucleic acid): a molecule similar to DNA (qv), which helps in the process of decoding the genetic information carried by DNA.
Safety: Practical certainty that injury will not result from a hazard under defined conditions.
SCF: The European Commission's Scientific Committee on Food (formerly the Scientific Committee for Food).
Single nucleotide polymorphism (SNP): DNA sequence variations that occur when a single nucleotide in the genome sequence is altered. For example, a SNP might change the DNA sequence AAGGCTAA to ATGGCTAA. By convention, SNPs occur in at least 1% of the population.
Sister chromatid exchange (SCE): Exchange of genetic material between two sub-units of a replicated chromosome.
Stakeholder: A person or organisation representing the interests and opinions
of a group with an interest in the outcome of (for example) a review or policy decision.
Suppressor gene: A gene which helps to reverse the effects of damage to an individual's genetic material, typically effects which might lead to uncontrolled cell growth (as would occur in cancer). A suppressor gene may, for example, code for a protein which checks genes for misspellings, and/or which triggers a cell's self-destruction if too much DNA damage has occurred.
Surfactant: Also called: surface-active agent. A substance, such as a detergent, that can reduce the surface tension of a liquid and thus allow it to foam or penetrate solids; a wetting agent.
Systematic review: A review that has been prepared using a documented systematic approach to minimising biases and random errors.
TDI: See 'Tolerable Daily Intake'.
Teratogen: A substance which, when administered to a pregnant woman or animal, can cause congenital malformations (structural defects) in the baby or offspring.
Testicular Dysgenesis Syndrome (TDS): The hypothesis that maldevelopment (dysgenesis) of the fetal testis results in hormonal or other malfunctions of the testicular somatic cells which in turn predispose a male to the disorders that comprise the TDS, i.e. congenital malformations (cryptorchidism and hypospadias) in babies and testis cancer and low sperm counts in young men.
Threshold: Dose or exposure concentration below which an effect is not expected.
Tolerable Daily Intake (TDI): An estimate of the amount of contaminant, expressed on a body weight basis (e.g. mg/kg bodyweight), that can be ingested daily over a lifetime without appreciable health risk.
Toxic Equivalency Factor (TEF): A measure of relative toxicological potency of a chemical compared to a well characterised reference compound. TEFs can be used to sum the toxicological potency of a mixture of chemicals which are all members of the same chemical class, having common structural, toxicological and biochemical properties. TEF systems have been published for the chlorinated dibenzodioxins, dibenzofurans and dioxin-like polychlorinated biphenyls, and for polycyclic aromatic hydrocarbons.
Total Toxic Equivalent (TEQ): Is a method of comparing the total relative toxicological potency within a sample. It is calculated as the sum of the products of the concentration of each congener multiplied by the toxic equivalency factor (TEF).
Toxicodynamics: The process of interaction of chemical substances with target sites and the subsequent reactions leading to adverse effects.
Toxicogenic: producing or capable of producing a toxin.
Toxicogenomics: A new scientific subdiscipline that combines the emerging technologies of genomics and bioinformatics to identify and characterise mechanisms of action of known and suspected toxicants. Currently, the premier toxicogenomic tools are the DNA microarray and the DNA chip, which are used for the simultaneous monitoring of expression levels of hundreds to thousands of genes.
Toxicokinetics: The description of the fate of chemicals in the body, including a mathematical account of their absorption, distribution, metabolism and excretion. (see pharmacokinetics)
Transcription: the process during which the information in a length of DNA (qv) is used to construct an mRNA (qv) molecule.
Transcriptomics: Techniques available to identify mRNA from actively transcribed genes.
Transfer RNA (tRNA): RNA molecules which bond with amino acids and transfer them to ribosome’s, where protein synthesis is completed.
Transfection: A process by which the genetic material carried by an individual cell is altered by incorporation of exogenous DNA into its genome.
Transgenic: Genetically modified to contain genetic material from another species (see also genetically modified organism).
Transgenic animal models: Animals which have extra (exogenous) fragments of DNA incorporated into their genomes. This may include reporter genes to assess in-vivo effects such as mutagenicity in transgenic mice containing a recoverable bacterial gene (lacZ or lac I). Other transgenic animals may have alterations of specific genes believed to be involved in disease processes (e.g. cancer). For example strains of mice have been bred which carry an inactivated copy of the p53 tumour suppressor gene (qv) -, or an activated form of the ras oncogene which may enhance their susceptibility of the mice to certain types of carcinogenic chemicals.
Translation: In molecular biology, the process during which the information in mRNA molecules is used to construct proteins.
Tumour (Synonym - neoplasm): A mass of abnormal, disorganised cells, arising from pre-existing tissue, which are characterised by excessive and uncoordinated proliferation and by abnormal differentiation. Benign tumours show a close morphological resemblance to their tissue of origin; grow in a slow expansile fashion; and form circumscribed and (usually) encapsulated masses. They may stop growing and they may regress. Benign tumours do not infiltrate through local tissues and they do not metastasise (qv). They are rarely fatal. Malignant tumours (synonym - cancer) resemble their parent tissues less closely and are composed of increasingly abnormal cells in terms of their form and function. Well differentiated examples still retain recognisable features of their tissue of origin but these characteristics are progressively lost in moderately and poorly differentiated malignancies: undifferentiated or anaplastic tumours are composed of cells which resemble no known normal tissue. Most malignant tumours grow rapidly, spread progressively through adjacent tissues and metastasise to distant sites. Tumours are conventionally classified according to the anatomical site of the primary tumour and its microscopical appearance, rather than by cause. Some common examples of nomenclature are as follows:
- Tumours arising from epithelia (qv): benign - adenomas, papillomas; malignant - adenocarcinomas, papillary carcinomas.
- Tumours arising from connective tissues such as fat, cartilage or bone: benign - lipomas, chondromas, osteomas; malignant - fibrosarcomas, liposarcomas, chondrosarcomas, osteosarcomas.
- Tumours arising from lymphoid tissues are malignant and are called lymphomas (qv); they are often multifocal. Malignant proliferations of bone marrow cells are called leukaemias.
Benign tumours may evolve to the corresponding malignant tumours; examples involve the adenoma to carcinoma sequence in the large bowel in humans, and the papilloma to carcinoma sequence in mouse skin.
Tumour initiation: A term originally used to describe and explain observations made in laboratory models of multistage carcinogenesis, principally involving repeated applications of chemicals to the skin of mice. Initiation, in such contexts, was the first step whereby small numbers of cells were irreversibly changed, or initiated. Subsequent, separate events (see tumour promotion) resulted in the development of tumours. It is now recognised that these early, irreversible heritable changes in initiated cells were due to genotoxic damage, usually in the form of somatic mutations and the initiators used in these experimental models can be regarded as genotoxic carcinogens (qv).
Tumour promotion: An increasingly confusing term, originally used, like ‘tumour initiation’ to describe events in multistage carcinogenesis in experimental animals. In that context, promotion is regarded as the protracted process whereby initiated cells undergo clonal expansion to form overt tumours. The mechanisms of clonal expansion are diverse, but include direct stimulation of cell proliferation, repeated cycles of cell damage and cell regeneration and release of cells from normal growth-controlling mechanisms. Initiating and promoting agents were originally regarded as separate categories, but the distinction between them is becoming increasingly hard to sustain. The various modes of promotion are non-genotoxic, but it is incorrect to conclude that ‘non-genotoxic carcinogen’ (qv) and ‘promoter’ are synonymous.
Uncertainty factor: Value used in extrapolation from experimental animals to man (assuming that man may be more sensitive) or from selected individuals to the general population: for example, a value applied to the NOAEL to derive an ADI or TDI. The value depends on the size and type of population to be protected and the quality of the toxicological information available.
Unscheduled DNA Synthesis (UDS): DNA synthesis that occurs at some stage in the cell cycle other than the S period (the normal or 'scheduled' DNA synthesis period), in response to DNA damage. It is usually associated with DNA repair.
Volume of distribution: Apparent volume of fluid required to contain the total amount of a substance in the body at the same concentration as that present in the plasma, assuming equilibrium has been attained.
WHO-TEQs: The system of Toxic Equivalency Factors (TEFs) used in the UK and a number of other countries to express the concentrations of the less toxic dioxin-like compounds (16 PCDDs/PCDFs and 12 PCBs) as a concentration equivalent to the most toxic dioxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is that set by the World Health Organisation (WHO), and the resulting overall concentrations are referred to as WHO-TEQs (Total toxic equivalents).
Xenobiotic: A chemical foreign to the biologic system.
Xenoestrogen: A 'foreign' compound with estrogenic activity (see estrogen).