Glossary [chapter]

A Textbook of Modern Toxicology  
GLOSSARY 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). 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. acetylator phenotype Variation
more » ... the expression of N-acetyltransferase isoforms in humans gives rise to two subpopulations-fast and slow acetylators. Slow acetylators are more susceptible to the toxic effects of toxicants that are detoxified by acetylation. acid deposition 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. Sulfuric acid from sulfur 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. 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 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 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. See also eye irritation tests; LC50; and LD50. 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 two weeks. GLOSSARY 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. Ah locus A gene(s) controlling the trait of responsiveness for induction of enzymes by aromatic hydrocarbons. In addition to aromatic hydrocarbons such as the polycyclics, the chlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls, as well as the brominated biphenyls, are involved. This trait, originally defined by studies of induction of hepatic aryl hydrocarbon hydroxylase activity following 3-methylcholanthrene treatment, is inherited by simple autosomal dominance in crosses and backcrosses between C57BL/6 (Ah-responsive) and DBA/2 (Ah-nonresponsive) mice. Ah receptor (AHR) A protein coded for by a gene of the Ah locus. The initial location of the Ah receptor is believed to be in the cytosol and, after binding to a ligand such as TCDD, is transported to the nucleus. Binding of aromatic hydrocarbons to the Ah receptor of mice is a prerequisite for the induction of many xenobiotic metabolizing enzymes, as well as for two responses to TCDD; epidermal hyperplasia and thymic atrophy. Ah-responsive mice have a high-affinity receptor, whereas the Ah-nonresponsive mice have a low-affinity receptor. air pollution In general, the principal air pollutants are carbon monoxide, oxides of nitrogen, oxides of sulfur, hydrocarbons, and particulates. The principal sources are transportation, industrial processes, 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 peroxyacetyl nitrate, acrolein, 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. alkylating agents These are chemicals that can add alkyl groups to DNA, a reaction that can result either in mispairing of bases or in chromosome breaks. The mechanism of the reaction involves the formation of a reactive carbonium ion that combines with electron-rich bases in DNA. Thus alkylating agents such as dimethylnitrosomine are frequently carcinogens and/or mutagens. Ames test An in vitro test for mutagenicity utilizing mutant strains of the bacterium Salmonella typhimurium that is used as a preliminary screen of chemicals for assessing potential carcinogenicity. Several strains are available that cannot grow in the absence of histidine because of metabolic defects in histidine biosynthesis. Mutagens and presumed carcinogens can cause mutations that enable the strains to regain
doi:10.1002/0471646776.gloss fatcat:cy7frh6dnnectjrm4dsz2sfu74