Large (10-20 μm diameter) amoeboid and phagocytic cell found in many tissues, especially in areas of inflammation, derived from blood monocytes and playing an important role in host defense mechanisms.
macroscopic (gross) pathology
Study of changes associated with disease that are visible to the naked eye without the need for a microscope.
Mad Hatter syndrome
Magnusson and Kligman test
See guinea-pig maximization test
mainstream smoke (tobacco smoking)
Smoke that is inhaled by the smoker.
Vague feeling of bodily discomfort.
Emotional disorder (mental illness) characterized by an expansive and elated state (euphoria), rapid speech, flight of ideas, decreased need for sleep, distractibility, grandiosity, poor judgment and increased motor activity.
margin of safety (MOS)
See margin of exposure
mass median diameter
Diameter of a spherical particle with the median mass of all the particles in a population.
material safety data sheet (MSDS)
Compilation of information required under the US OSHA Hazard Communication Standard on the identity of hazardous substances, health and physical hazards, exposure limits, and precautions.
maximum allowable (admissible, acceptable)
Regulatory value defining the concentration that if inhaled daily (in the case of work people for 8 hours with a working week of 40 hours, in the case of the general population 24 hours) does not, in the present state of knowledge, appear capable of causing appreciable harm, however long delayed during the working life or during subsequent life or in subsequent generations.
maximum average daily concentration of an atmospheric
peak daily average concentration of an air pollutant
Highest of the average daily concentrations recorded at a definite point of measurement during a certain period of observation.
maximum contaminant level (MCL)
Under the Safe Drinking Water Act (USA), primary MCL is a regulatory concentration for drinking water which takes into account both adverse effects (including sensitive populations) and technological feasibility (including natural background levels): secondary MCL is a regulatory concentration based on “welfare”, such as taste and staining, rather than health, but also takes into account technical feasibility.
Note: MCL Goals (MCLG) under the Safe Drinking Water Act do not consider feasibility and are zero for all human and animal carcinogens.
maximum exposure limit (MEL)
Occupational exposure limit legally defined in GB under COSHH as the maximum concentration of an airborne substance, averaged over a reference period, to which employees may be exposed by inhalation under any circumstances, and set on the advice of the HSC Advisory Committee on Toxic Substances.
maximum permissible concentration (MPC)
See maximum allowable concentration
maximum permissible daily dose
Maximum daily dose of substance whose penetration into a human body during a lifetime will not cause diseases or health hazards that can be detected by current investigation methods and will not adversely affect future generations.
maximum residue limit for pesticide residues
Maximum contents of a pesticide residue (expressed as mg kg-1 fresh weight) recommended by the Codex Alimentarius Commission to be legally permitted in or on food commodities and animal feeds.
Note: MRL’s are based on data obtained following good agricultural practice and foods derived from commodities that comply with the respective MRL's are intended to be toxicologically acceptable.
maximum residue limit for veterinary drugs
Maximum contents of a drug residue (expressed as mg kg-1 or μg kg-1 fresh weight) recommended by the Codex Alimentarius Commission to be legally permitted or recognized as acceptable in or on food commodities and animal feeds.
Note: The MRL is based on the type and amount of residue considered to be without any toxicological hazard for human health as expressed by the acceptable daily intake (ADI) or on the basis of a temporary ADI that uses an additional uncertainty factor. It also takes into account other relevant public health risks as well as food technological aspects.
maximum tolerable concentration
Highest concentration of a substance in an environmental medium that does not cause death of test organisms or species (denoted by LC0).
maximum tolerable dose (MTD)
Highest amount of a substance that, when introduced into the body, does not kill test animals (denoted by LD0).
maximum tolerated dose (MTD)
High dose used in chronic toxicity testing that is expected on the basis of an adequate subchronic study to produce limited toxicity when administered for the duration of the test period.
Note 1: It should not induce:
(a) overt toxicity, for example appreciable death of cells or organ dysfunction, or
(b) toxic manifestations that are predicted materially to reduce the life span of the animals except as the result of neoplastic development or
(c) 10% or greater retardation of body weight gain as compared with control animals.
Note 2: In some studies, toxicity that could interfere with a carcinogenic effect is specifically excluded from consideration.
Average lifetime of a molecular, atomic, or nuclear system in a specified state.
Note: For an exponentially decaying system, it is the average time for the number of molecules, atoms or nuclei in a specified state to decrease by a factor of e, the base of natural logarithms.
mean residence time (in
Average time a drug molecule remains in the body or an organ after rapid intravenous injection.
Note 1: Like clearance, its value is independent of dose.
Note 2: After an intravenous bolus:
tr = Am/ A
where tr is the MRT, A is the area under the plasma concentration-time curve, and Am is the area under the moment curve.
Note 3: For a drug with one-compartment distribution characteristics, MRT equals the reciprocal of the elimination rate constant.
median effective concentration
Statistically derived median concentration of a substance in an environmental medium expected to produce a certain effect in 50% of test organisms in a given population under a defined set of conditions.
Note: ECn refers to the median concentration that is effective in n% of the test population.
median effective dose (ED50)
Statistically derived median dose of a chemical or physical agent (radiation) expected to produce a certain effect in 50% of test organisms in a given population or to produce a half-maximal effect in a biological system under a defined set of conditions.
Note: EDn refers to the median dose that is effective in n% of the test population.
median lethal concentration
Statistically derived median concentration of a substance in an environmental medium expected to kill 50% of organisms in a given population under a defined set of conditions.
median lethal dose (LD50)
Statistically derived median dose of a chemical or physical agent (radiation) expected to kill 50% of organisms in a given population under a defined set of conditions.
median lethal time (TL50)
Statistically derived median time interval during which 50% of a given population may be expected to die following acute administration of a chemical or physical agent (radiation) at a given concentration under a defined set of conditions.
median narcotic concentration
Statistically derived median concentration of a substance in an environmental medium expected to cause narcotic conditions in 50 % of a given population under a defined set of conditions.
median narcotic dose
Statistically derived dose of a substance expected to cause narcotic conditions in 50 % of test animals under a defined set of conditions.
Process of “reductive” cell division, occurring in the production of gametes, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species.
See also miosis.
Mad Hatter syndrome
Chronic poisoning caused by exposure to mercury, often by breathing its vapor but also by skin absorption and, less commonly, by ingestion.
Note: Central nervous system damage usually predominates.
Malignant tumor of the mesothelium of the pleura, pericardium or peritoneum, that may be caused by exposure to asbestos fibers and some other fibers.
metabolic half life
metabolic half time
Time required for one half of the quantity of a substance in the body to be metabolized.
Note: This definition assumes that the final quantity in the body is zero. See half life.
Analysis and theoretical reconstruction of the way in which the body deals with a specific substance, showing the proportion of the intake that is absorbed, the proportion that is stored and in what tissues, the rate of breakdown in the body and the subsequent fate of the metabolic products, and the rate at which it is eliminated (see elimination) by different organs as unchanged substance or metabolites.
Biotransformation of a substance that takes place within a living organism.
Intermediate or product resulting from metabolism.
Evaluation of cells, tissues or biological fluids for changes in metabolite levels that follow exposure to a given substance, in order to determine the metabolic processes involved, to evaluate the disruption in intermediary metabolic processes that results from exposure to that substance, or to determine the part of the genome that is responsible for the changes.
Note: Although “metabolomics” and “metabonomics” are frequently used as synonyms, there is a growing consensus that there is a difference in that “metabolomics” places a greater emphasis on comprehensive metabolic profiling, while “metabonomics” is used to describe multiple (but not necessarily comprehensive) metabolic changes caused by a biological perturbation.
Presence of methaemoglobin in the blood in greater than normal proportion.
Substance capable of oxidizing directly or indirectly the iron(II) in hemoglobin to iron(III) to form methemoglobin.
Substance concentration of
substrate at which the rate of reaction is
equal to one half of the limiting rate (maximum rate).
Note: Also called the Michaelis concentration. The Michaelis constant (Michaelis concentration) may be used only when Michaelis-Menten kinetics is obeyed.
Description of the dependence of an initial rate of reaction upon the concentration of a substrate S that is present in large excess over the concentration of an enzyme or other catalyst (or reagent) E with the appearance of saturation behavior following the Michaelis-Menten equation:
n = V[S]o/(KM + [S])
where v is the observed initial rate, V is
its limiting value at substrate saturation (i.e. [S] > >
KM), and KM the substrate
when v = V/2. The definition is experimental,
i.e. it applies to any reaction that follows an equation of this
general form. The symbols Vmax or
vmax are sometimes used for V.
Note 1. The parameters V and KM (the ‘Michaelis constant’) of the equation can be evaluated from the slope and intercept of a linear plot of 1/v vs. 1/[S] (‘Lineweaver-Burk plot’) or from slope and intercept of a linear plot of v vs. v/[S] (‘Eadie-Hofstee plot’).
Note 2. A Michaelis-Menten equation is also applicable to the condition where E is present in large excess, in which case the total concentration [E]o appears in the equation instead of [S]o.
Note 3. The term has sometimes been used to describe reactions that proceed according to the scheme:
in which case KM = (k–1 + kcat)/k1 (Briggs-Haldane conditions). It has more usually been applied only to the special case in which k–1 >> kcat and KM = k–1/k1 = KS, the dissociation constant of the complex. In this case KM is a true dissociation constant (Michaelis-Menten conditions).
Simplest mechanism that explains Michaelis-Menten kinetics.
Note 1: According to the mechanism, a substrate S first combines with a molecule of enzyme E, and this process is followed by a step in which the enzyme-substrate complex ES breaks down (sometimes with the participation of the solvent) into enzyme and reaction products:
If, as is usual, the substrate S is present in great excess of the enzyme it can be shown that steady-state conditions apply, and that the rate equation is:
where [E]o , [S]o are the total
enzyme and substrate. This equation is of the required general
form of the Michaelis-Menten equation.
Note 2: Other, more complicated, mechanisms lead to the Michaelis-Menten equation, adherence to which therefore does not require that the Michaelis-Menten mechanism applies.
Chronic presence of albumin in slight excess in urine.
Grid of nucleic acid molecules of known sequence linked to a solid substrate, which can be probed with a sample containing either messenger RNA or complementary DNA from a cell or tissue to reveal changes in gene expression relative to a control sample.
Note: Micro-array technology, which is also known as “DNA gene chip” technology, allows the expression of many thousands of genes to be assessed in a single experiment.
experimental model ecosystem
Artificial test system that simulates major characteristics of the natural environment for the purposes of ecotoxicological assessment.
Note: Such a system would commonly have a terrestrial phase, with substrate, plants and herbivores, and an aquatic phase, with vertebrates, invertebrates and plankton. The term “mesocosm” implies a more complex and larger system than the term “microcosm” but the distinction is not clearly defined.
Early or subclinical effects of exposure to elemental mercury detected at the low exposure levels.
Test for mutagenicity in which animals are treated with a test agent after which time the frequency of micronucleated cells is determined; if a test group shows significantly increased levels of micronucleated cells compared to a control group, the chemical is considered capable of inducing chromosomal damage.
Chronic presence of microprotein (alpha-1 and beta-2 microglobulin) in blood indicating proximal renal tubule damage.
Artefactual spherical particle, not present in the living cell, derived from pieces of the endoplasmic reticulum present in homogenates of tissues or cells.
Note: Microsomes sediment from such homogenates (usually the S9 fraction) when centrifuged at 100 000 g for 60 minutes: the microsomal fraction obtained in this way is often used as a source of mono-oxygenase enzymes.
Neurological disease caused by methylmercury, first seen in subjects ingesting contaminated fish from Minamata Bay in Japan.
Complete conversion of organic substances to inorganic derivatives, often visible as microscopic deposits which may be associated with damage to soft tissue, e.g., in the kidney.
minimal risk level (MRL)
Estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration of exposure: this substance specific estimate is used by ATSDR health assessors to identify contaminants and potential health effects that may be of concern at hazardous waste sites.
minimum lethal concentration
Lowest concentration of a toxic substance in an environmental medium that kills individual organisms or test species under a defined set of conditions.
minimum lethal dose
Lowest amount of a substance that, when introduced into the body, may cause death to individual species of test animals under a defined set of conditions.
Liquid substances capable of mixing without separation into two phases; refers to liquid mixtures.
Substance used for the control of mites.
mitochondri/on sing., /a
Eukaryote cytoplasmic organelle that is bounded by an outer membrane and an inner membrane; the inner membrane has folds called cristae that are the centre of ATP synthesis in oxidative phosphorylation in the animal cell and supplement ATP synthesis by the chloroplasts in photosynthetic cells.
Note: The mitochondrial matrix within the inner membrane contains ribosomes, many oxidative enzymes, and a circular DNA molecule that carries the genetic information for a number of these enzymes.
mixed function oxidase (MFO)
Substance intended to kill mollusks.
Continuous or repeated observation, measurement, and evaluation of health and (or) environmental or technical data for defined purposes, according to prearranged schedules in space and time, using comparable methods for sensing and data collection.
Note: Evaluation requires comparison with appropriate reference values based on knowledge of the probable relationship between ambient exposure and adverse effects.
Pertaining to a specific protein from a single clone of cells, all molecules of this protein being the same.
Enzyme that catalyses reactions between an organic compound and molecular oxygen in which one atom of the oxygen molecule is incorporated into the organic compound and one atom is reduced to water; involved in the metabolism of many natural and foreign compounds giving both unreactive products and products of different or increased toxicity from that of the parent compound.
Note: Such enzymes are the main catalysts of phase 1 reactions in the metabolism of xenobiotics by the endoplasmic reticulum or by preparations of microsomes.
Monte Carlo simulation
Analysis of a sequence of events using random numbers to generate possible outcomes in an iterative process.
Any departure, subjective or objective, from a state of physiological or psychological well-being: in this sense, “sickness”, “illness”, and “morbid condition” are similarly defined and synonymous.
Substance that fixes a dyestuff in or on a material by combining with the dye to form an insoluble compound, used to fix or intensify stains in a tissue or cell preparation.
See death rate
Investigation dealing with death rates or proportion of deaths attributed to specific causes as a measure of response.
Mulliken population analysis
Partitioning scheme based on the use of density and overlap matrices, at one time used for allocating the electrons of a molecular entity in some fractional manner among its various parts (atoms, bonds, orbitals).
Illness with pathogenesis dependent on complex interplay of genetic and (or) environmental factors.
multiple chemical sensitivity (MCS)
idiopathic environmental intolerance
Intolerance condition attributed to extreme sensitivity to various environmental chemicals, found in air, food, water, building materials, or fabrics.
Note: This syndrome is characterized by the patient's belief that his or her symptoms are caused by very low-level exposure to environmental chemicals. The term “chemical” is used to refer broadly to many natural and man-made chemical agents, some of which have several chemical constituents. Several theories have been advanced to explain the cause of multiple chemical sensitivity, including allergy, toxic effects and neurobiologic sensitization. There is insufficient scientific evidence to confirm a relationship between any of these possible causes and symptoms.
multiple (or multiphasic) screening
Procedure that has evolved by combining single screening tests, and is the logical corollary of mass screening.
Note 1: Where much time and effort have been spent by a population in attending for a single test such as mass radiography, it is natural to consider the economy of offering other tests at the same time.
Note 2: Multiple (or multiphasic) screening implies the administration of a number of tests, in combination, to large groups of people.
Of a cell, capable of giving rise to several different kinds of structure or types of cell.
multistage cluster sampling
Cluster sampling with more than two stages, each sampling being made on aggregates (or clusters) in which the clusters already obtained by the preceding sampling have been divided.
Dose -response model for cancer death estimation of the form
P = 1 - exp[-(qo + q1d1+ q2d2 + … +qkdk)]
where P is the probability of cancer death from a
continuous dose rate,
di, of group (or stage) i = 0, 1, 2... , the
q's are constants, and k is the number of dose groups
(or, if less than the number of dose groups, k is the
number of biological stages believed to be required in the
With the multistage model, it is assumed that cancer is
initiated by cell mutations in a finite series of steps.
Type of sampling in which the sample is selected by stages, the sampling units at each stage being subsampled from the larger units chosen at the previous stage.
Set of statistical tools to analyse data matrices using regression and (or) pattern recognition techniques.
Of or belonging to the family of rats and mice (Muridae).
Ability of a physical, chemical, or biological agent to induce (or generate) heritable changes (mutations) in the genotype in a cell as a consequence of alterations or loss of genes or chromosomes (or parts thereof).
Any relatively stable heritable change in genetic material that may be a chemical transformation of an individual gene (gene or point mutation), altering its function, or a rearrangement, gain or loss of part of a chromosome, that may be microscopically visible (chromosomal mutation).
Note: Mutation can be either germinal, and inherited by subsequent generations, or somatic and passed through cell lineage by cell division.
Toxin produced by a fungus.
Note: Examples are aflatoxins, tricothecenes, ochratoxin and patulin.
Extreme dilation of the pupil of the eye, either as a result of normal physiological response or in response to a chemical exposure.
Reduction of bone marrow activity leading to a lower concentration of platelets, red cells and white cells in the blood.