IUPAC Glossary of Terms Used in Toxicology – N
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macrophage
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
See mercurialism
Magnusson and Kligman test
See guinea-pig
maximization test
mainstream smoke (tobacco smoking)
Smoke that is inhaled by the smoker.
malaise
Vague feeling of bodily discomfort.
malignancy
Population of cells showing both uncontrolled growth and a
tendency to invade and destroy other tissues.
Note: A malignancy is life-threatening.
malignant
antonym benign
- Tending to become progressively worse and to result in death if not treated.
- In cancer, cells showing both uncontrolled growth and a tendency to invade and destroy other tissues.
mania
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 exposure (MOE)
Ratio of the no-observed-adverse-effect level
(NOAEL) to the theoretical or estimated exposure dose (EED) or
concentration (EEC).
margin of safety (MOS)
See margin of
exposure
mass mean diameter
Diameter of a spherical particle with a mass equal to the mean
mass of all the particles in a population.
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)
concentration (MAC)
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
pollutant
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 permissible level (MPL)
Level, usually a combination of time and concentration, beyond which
any exposure of humans
to a chemical or physical agent in their immediate environment is
unsafe.
maximum residue limit for pesticide residues
(MRL)
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
(MRL)
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
(MTC)
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 tolerable exposure level
(MTEL)
Maximum amount (dose) or concentration of a substance
to which an organism can be exposed without leading to an
adverse effect
after prolonged exposure time.
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.
maximum velocity,
Vmax
maximum rate
In Michaelis-Menten kinetics, the
maximum rate of conversion of a substrate when
its concentration
is not rate limiting.
[2]
mean life
mean time
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
pharmacokinetics) (MRT)
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.
After [2]
measurement uncertainty
See uncertainty
median effective concentration
(EC50)
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
(LC50)
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
(NC50)
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
(ND50)
Statistically derived dose of a substance expected to cause
narcotic
conditions in 50 % of test animals under a defined set of
conditions.
medicine
- Science and practice of diagnosing, treating, or preventing disease and other damage to the body or mind.
- Any drug or therapy used to treat disease or injury.
Note: Any substance may be used as a drug or a remedy; the end effect will depend on the dose.
meiosis
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.
mercurialism
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.
mesocosm
See microcosm
mesothelioma
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 activation
bio-activation
Biotransformation of a
substance to a more biologically active derivative.
[2]
metabolic enzymes
Proteins that catalyse chemical transformations of body
constituents and, in more common usage, of xenobiotics.
[2]
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.
metabolic model
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.
metabolic transformation
Biotransformation of a
substance that takes place within a living organism.
- Sum total of all physical and chemical processes that take place within an organism from uptake to elimination.
- In a narrower sense, the physical and chemical changes that take place in a substance within an organism, including biotransformation to metabolites.
metabolite
Intermediate or product resulting from metabolism.
metabolomics
See metabonomics
metabonomics
metabolomics
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.
After [2]
metaplasia
Abnormal transformation of an adult, fully differentiated tissue
of one kind into a differentiated tissue of another kind.
metastasis
- Movement of bacteria or body cells, especially cancer cells, from one part of the body to another, resulting in change in location of a disease or of its symptoms from one part of the body to another.
- Growth of pathogenic micro-organisms or of abnormal cells distant from the site of their origin in the body.
methaemoglobin
See methemoglobin
methemoglobin
methaemoglobin
Derivative of hemoglobin that is formed when the iron(II) in the
heme porphyrin is oxidized to iron(III); this derivative cannot
transport dioxygen.
methemoglobinaemia
methaemoglobinaemia
Presence of methaemoglobin in the blood in greater than normal
proportion.
methemoglobin-forming substance
methaemoglobin-forming substance
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.
[2]
Michaelis-Menten kinetics
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
concentration
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).
See also rate-controlling
step
[3]
Michaelis-Menten mechanism
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
concentrations of
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.
[2]
micro-albuminuria
Chronic presence of albumin in slight excess in urine.
micro-array
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.
After [8]
microcosm
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.
micromercurialism
Early or subclinical effects of exposure to elemental
mercury detected at the low exposure levels.
micronucleus test
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.
microproteinaemia
Chronic presence of microprotein (alpha-1 and beta-2
microglobulin) in blood indicating proximal renal tubule
damage.
microsome
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.
micturitic
See diuretic
midstream sampling
Taking an aliquot
of a flowing liquid, such as urine, avoiding initial and terminal
flow periods which are likely to be unrepresentative.
[2]
Minamata disease
Neurological disease caused by methylmercury, first seen in
subjects ingesting contaminated fish from Minamata Bay in
Japan.
mineralization
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
(LCmin)
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
(LDmin)
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.
miosis
meiosis (obsolete)
myosis
Abnormal contraction of the pupil of the eye to less than 2
mm.
miscible
Liquid substances capable of mixing without separation into two
phases; refers to liquid mixtures.
miticide
Substance used for the control of mites.
mitochondri/on sing., /a
pl.
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.
mitogen
Substance that induces lymphocyte transformation
or, more generally, mitosis and
cell proliferation.
mitosis
Process by which a cell nucleus divides into two daughter nuclei,
each having the same genetic complement as the parent cell:
nuclear division is usually followed by cell division.
mixed function oxidase (MFO)
See mono-oxygenase
modifying factor (MF)
See safety factor,
uncertainty factor
molluskicide
limacide
molluscicide
Substance intended to kill mollusks.
monitoring
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.
monoclonal
Pertaining to a specific protein from a single clone of cells,
all molecules of this protein being the same.
monoclonal antibody
Antibody produced
by cloned cells derived from a single lymphocyte.
mono-oxygenase
mixed-function oxidase
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.
After [2]
morbidity
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.
morbidity rate
Term (to be avoided) used loosely to refer to incidence or prevalence rates of
disease.
morbidity survey
Method for the estimation of the prevalence and (or)
incidence of a
disease or diseases in a population.
mordant
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.
mortality
Death as studied in a given population or subpopulation.
Note: The word mortality is often used incorrectly instead of
mortality rate.
mortality rate
See death
rate
mortality study
Investigation dealing with death rates or proportion of deaths
attributed to specific causes as a measure of response.
mucociliary transport
Process of removal of particles from the bronchi of the lungs in
a mucus stream moved by cilia, thus contributing to uptake from the gastrointestinal
tract.
[2]
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).
[2]
multicompartment model
Product of a compartmental
analysis requiring more than two compartments.
[2]
multifactorial disease
Illness with pathogenesis dependent on complex interplay of
genetic and (or) environmental factors.
After [9]
- Toxicity test in which two to three generations of the test organism are exposed to the substance being assessed.
- Toxicity test in which only one generation is exposed and effects on subsequent generations are assessed.
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.
multipotent
Of a cell, capable of giving rise to several different kinds of
structure or types of cell.
[2]
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.
multistage model
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
carcinogenesis process).
With the multistage model, it is assumed that cancer is
initiated by cell mutations in a finite series of steps.
[2]
multistage sampling
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.
multivariate statistics
Set of statistical tools to analyse data matrices using
regression and (or) pattern recognition techniques.
[2]
murine
Of or belonging to the family of rats and mice (Muridae).
mutagen
Agent that can induce heritable changes (mutations) of the genotype in a cell as a
consequence of alterations in or loss of genetic material.
mutagenesis
Induction (or generation) of heritable changes (mutations) of the genotype in a cell as a
consequence of alterations or loss of genes or chromosomes (or parts
thereof).
mutagenicity
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).
mutation
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.
myalgia
Pain or tenderness in a muscle or group of muscles.
mycotoxin
Toxin produced by a fungus.
Note: Examples are aflatoxins, tricothecenes, ochratoxin and
patulin.
mydriasis
Extreme dilation of the pupil of the eye, either as a result of
normal physiological response or in response to a chemical
exposure.
myelosuppression
Reduction of bone marrow activity leading to a lower concentration of
platelets, red cells and white cells in the blood.