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Toxicological Effects of Methylmercury GLOSSARY Absorbed dose – The amount of a substance that penetrates an exposed organism's absorption barriers (e.g., skin, lung tissue, gastrointestinal tract) through physical or biological processes. The term is synonymous with internal dose. Administered dose – The amount of a substance given to a test subject (human or animal) in determining dose-response relationships, especially through ingestion or inhalation. In exposure assessment, since exposure to chemicals is usually inadvertent, this quantity is called potential dose. Adverse effect – Any effect that produces functional impairment and/or a pathological lesion that may affect the performance of the whole organism, or that reduces an organisms ability to respond to an additional challenge (Stara et al. 1985) Anthropogenic – Of human origin. Applied dose – The amount of a substance in contact with the primary absorption boundaries of an organism (e.g, skin, lung, gastrointestinal tract) and available for absorption. Autoimmunity – A condition resulting from the production of autoantibodies, characterized by cell-mediated or humoral immunological responses to antigens of one's own body, sometimes with damage to normal components of the body. Benchmark dose analysis – A technique for quantitative assessment of noncancer health effects. Benchmark dose – An exposure level that corresponds to a statistical
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Toxicological Effects of Methylmercury lower bound on a standard probability of an effect, such as 10% of people affected. Bioaccumulation – An increase in concentration in living organisms as they take in contaminated air, water, or food because the substances are very slowly metabolized or excreted. Bias – Any effect tending to produce results that depart systematically from the true values. Two principle forms of bias in human epidemiological studies are misclassification, when there are misassignments in exposure or adverse outcome, and selection, in which subjects selected for study differ systematically from those not selected. Bioactivation – A metabolic process wherein an inactive chemical is converted to an active one in the body. Bioavailability – 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. Biomarker of Effect – A measurable biochemical, physiological, or other alteration within an organism that, depending on magnitude, can be recognized as an established or potential health impairment or disease. Biomarker of Exposure – An exogenous substance, the metabolite(s) or the product of interactions between a xenobiotic agent and some target molecule or cell that is measured in a compartment within an organism. Biologically effective dose – The amount of the deposited or absorbed contaminant that reaches the cells or target site where an adverse effect occurs or where an interaction of that contaminant with a membrane surface occurs. Biotransformation A series of chemical alterations within the body whereby a foreign substance is transformed to a more or less toxic substance. Case-control study – An epidemiological study in which persons are selected because they have a specific disease or other outcome (cases) and are compared to a control (referent comparison) group without the disease to evaluate whether there is a difference in their reported frequency of exposure to possible disease risk factors. Also termed a retrospective study or case referent study. Chronic exposure – Multiple exposures occurring over an extended
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Toxicological Effects of Methylmercury period of time or over a significant fraction of an animal's or human's lifetime (Usually seven years to a lifetime.) Chronic toxicity – The capacity of a substance to cause long-term poisonous health effects in humans, animals, fish, and other organisms. Cohort study – An epidemiological study in which a defined group of persons known to be exposed to a potential disease risk factor is followed over time and compared to a group of persons who were not known to be exposed to the potential risk factor to evaluate the differences in rates of the outcome. Also termed a prospective study, followup study, incidence study, retrospective cohort, or historical cohort study. Concentration (C) – The total quantity of substance present in a given unit volume (of gas or liquid). It may be expressed in any unit or mass per unit of volume such as milligrams per cubic meter (mg/m3), or as volume per volume such as parts per million (ppm). Confidence interval (95%) – A range of values for the effect estimate within which the true value is though to lie with a 95% level of confidence. Confounder (confounding factor) – A factor that is associated with both the exposure and outcome of interest and can distort the apparent magnitude of the effect of the study factor. Developmental toxicity – The occurrence of adverse effects on the developing organism that may result from exposure to a chemical prior to conception (either parent), during prenatal development, or postnatally to the time of sexual maturation. Adverse development effects may be detected at any point in the life span of the organism. Dose – The amount of a risk agent that enters or interacts with organisms. An administered dose is the amount of substance administered to an animal or human, usually measured in milligrams per kilogram of body weight; milligrams per square meter of body surface area; or parts per million of the diet, drinking water, or ambient air. An effective dose is the amount of the substance reaching the target organ. Dose estimation – The process by which a delivered dose is estimated from an exposure dose or from a biomarker of exposures. Dose-response assessment – The determination of the relationship between the magnitude of administered, applied, or internal dose and specific biological response. Response can be expresses as measured or
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Toxicological Effects of Methylmercury observed incidence, percent response in groups of subjects (or populations), or the probability of occurrence of a response in a population. Dose-response curve – A graphical representation of the quantitative relationship between administered, applied, or internal dose of a chemical or agent, and a specific biological response to that chemical or agent. Dose-response model – A mathematical description of the relationship between exposure levels and the incidence rates of an effect. Dose-response relationship – A relationship between the amount of an agent (either administered, absorbed, or believed to be effective) and changes in certain aspects of the biological system (usually toxic effects), apparently in response to the agent. End points of toxicity – Adverse effects elicited as a result of exposure to a substance. Epidemiology – The core public health science, investigating the causes and risk factors of disease and injury in populations and the potential to reduce such disease burdens. Exposure – An event that occurs when there is contact at a boundary between a human and the environment with a contaminant of a specific concentration for an interval of time; the units of exposure are concentration multiplied by time. Exposure assessment – The determination or estimation (qualitative or quantitative) of the magnitude, frequency, duration, and route of exposure. Exposure dose – The level of contaminant in the air, water, or soil to which people are actually exposed. Genotoxic – Capable of altering the structure of DNA and causing mutations. Half-Life – The time required for the elimination of half a total dose from the body. Human health risk assessment – A process used to estimate the likelihood of adverse health outcomes of environmental exposures to chemicals. Immediate versus Delayed Toxicity – The immediate effects that occur or develop rapidly after a single administration or exposure of substances; delayed effects are those that occur after a lapse of some time.
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Toxicological Effects of Methylmercury These effects have also been referred to as acute and chronic, respectively. Immunological toxicity – The occurrence of adverse effects on the immune system that may result from exposure to environmental agents such as chemicals. Ingested dose – The amount of a substance consumed by an individual, usually expressed as amount per kilogram body weight over a given time period. Intake – The amount of material inhaled, absorbed through skin, or ingested during a specified period of time. Internal dose – In exposure assessment, the amount of a substance penetrating the absorption barriers (e.g., skin, lung tissue, gastrointestinal tract) of an organism through either physical or biological processes. Latency – Time from the first exposure of a chemical until the appearance of a toxic effect. Lifetime exposure – Total amount of exposure to a substance that a human would receive in a lifetime (usually assumed to be 75 years). Lipid solubility – The maximum concentration of a chemical that will dissolve in fatty substances. Lipid soluble substances are insoluble in water. They will very selectively disperse through the environment via intake in living tissue. Lowest-observed-adverse-effect level (LOAEL) – The lowest exposure level at which there are statistically or biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control group. Margin of exposure – A ratio defined by EPA as a dose derived from a tumor bioassay, epidemiological study, or biological marker study, such as the dose associated with a 10% response rate divided by an actual or projected human exposure. Mechanism of action – The way in which a substance (e.g., a chemical) exerts its toxic effect(s). Metabolism – All the biological reactions that take in a cell or an organism. Neurotoxicity – The occurrence of adverse effects on the nervous system following exposure to chemical. No-observed-adverse-effect level (NOAEL) – An exposure level at
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Toxicological Effects of Methylmercury which there are no statistically or biologically significant increases in the frequency or severity of adverse effects between the exposed population and its appropriate control; some effects may be produced at this level, but they are not considered as adverse, nor precursors to adverse effects. In an experiment with several NOAELs, the regulatory focus is primarily on the highest one, leading to the common usage of the term NOAEL as the highest exposure without adverse effect. Point of departure – An estimate or observed level of exposure or dose which is associated with an increase in adverse effect(s) in the study population. Examples of points of departure include NOAELs, LOAELs, BMDs, and BMDLs. Population at risk – a population subgroup that is more likely to be exposed to a chemical, or is more sensitive to the chemical, than is the general population. Power – The probability of detecting a specified difference in effect between experimental and control groups. Probability – A numerical value between 0 and 1 that represents the likelihood of something. Reference Dose (RfD) – an estimate (with uncertainty spanning perhaps an order of magnitude) of daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. Reproductive toxicity – The occurrence of adverse effects on the reproductive system that may result from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the related endocrine system. The manifestation of such toxicity may be noted as alterations in sexual behavior, fertility, pregnancy outcome, or modifications in other functions that are dependent on the integrity of this system. Risk – A measure of the probability that damage to life, health, property, and/or the environment will occur as a result of a given hazard. Risk assessment – An organized process used to describe and estimate the likelihood of adverse health outcomes from environmental exposures to chemicals. The four steps are hazard identification, dose-response assessment, exposure assessment, and risk characterization. Risk characterization – The last phase process of the risk assessment process that estimates the potential for adverse health or ecological
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Toxicological Effects of Methylmercury effects to occur from exposure to a stressor and evaluates the uncertainty involved. Risk management – The process of evaluating and selecting alterative regulatory and non-regulatory responses to risk. The selection process necessarily requires the consideration of legal, economic, and behavioral factors. Solubility – The amount of mass of a compound that will dissolve in a unit volume of solution. Aqueous Solubility is the maximum concentration of a chemical that will dissolve in pure water at a reference temperature. Standardized mortality ratio (SMR) – The ratio of observed deaths to expected deaths. Statistical control – The process by which that variability of measurements or of data outputs of a system is controlled to the extent necessary to produce stable and reproducible results. To say that measurements are under statistical control means that there is statistical evidence that the critical variables in the measurement process are being controlled to such an extent that the system yields data that are reproducible within well-defined limits. Susceptibility – The extent to which an individual is liable to infection or the effects of substances, such as toxicants, allergens, or other influences. The antithesis of resistance. Toxicant – A harmful substance or agent that may injury an exposed organism. Toxicity – A degree to which a substance or mixture of substances can harm humans or animals. Acute toxicity involves harmful effects in a organism through a single or short-term exposure. Chronic toxicity is the ability of a substance or mixture of substances to cause harmful effects over an extended period, usually upon repeated or continuous exposure sometimes lasting for the entire life of that exposed organism. Subchronic toxicity is the ability of the substance to cause effects for more than one year but less than the lifetime of the exposed organism. Toxicokinetics – The processes of absorption, distribution, metabolism, and excretion that occur between the time a toxic chemical enters the body and when it leaves.
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Toxicological Effects of Methylmercury Uncertainty - An estimate of the extent to which a risk estimate reflects reality. Uncertainty factor - One several, generally 10-fold factors, used in operationally deriving the Reference Dose (RfD) from experimental data. UF's are intended to account for (1) the variation in sensitivity among the members of the human population; (2) the uncertainty in extrapolating animal data to the case of humans; (3) the uncertainty in extrapolatingfrom data obtained in a study that is of less-than-lifetime exposure; and (4) the uncertainty in using LOAEL date rather than NOAEL data. Weight of the scientific evidence - Considerations involved in assessing the interpretation of published scientific information — quality of methods, ability of a study to detect adverse effects, consistency of results across studies, and biological plausibility of cause-and-effect relationships.
Representative terms from entire chapter: