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Dose Response Relationship

Toxicity

Definition of Dose
Dose is the amount of a substance
administered at one time.
Other parameters used to characterise the
exposure to xenobiotics include the number of
doses, frequency, and total time period of the
treatment.
For example: 10 mg DDT per day for 90 days

Doses of a Toxicant

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Fractionating a Total Dose

This usually decreases the probability that the total dose will cause
toxicity.
The reason for this is that the body often can repair the effect of
each sub-toxic dose if sufficient time passes before receiving the
next
dose.
In such a case, the total dose, harmful if received all at once, is
non-toxic when administered over a period of time.
For example, 30 mg
of strychnine swallowed at one time could be fatal to an adult
whereas 3
mg of strychnine swallowed each day for ten days would not be
fatal.

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For inhalation toxicity, air concentrations are

used for exposure values.
Thus, the LC50 is utilized which stands for
Lethal Concentration 50%, the calculated
concentration of a gas lethal to 50% of a
group.
Occasionally LC0 and LC10 are also used.

Effective Doses (EDs)

Toxic Doses (TDs)

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Concept of Lethal Dose

Basic Concept of Lethal dose or concentration
Median Lethal Dose Concept
Animal Toxicity Testing

Toxicology testing
This is also known as safety testing, is conducted by
pharmaceutical companies testing drugs.
According to 2005 EU figures, around one million animals are
used every year in Europe in toxicology tests; which are about
10% of all procedures.
According to Nature, 5,000 animals are used for each
chemical being tested, with 12,000 needed to test pesticides.
The tests are conducted without anaesthesia, because
interactions between drugs can affect how animals detoxify
chemicals, and may interfere with the results.

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Lethal Dose and Lethal Concentration

LD
LC
For gases and aerosols, lethal concentration
(mg/m or ppm, parts per million) is the
analogous concept, although this also depends
on the of exposure, which has to be included in
the definition.
The lowest known lethal dose, derived from an
individual case of poisoning, is abbreviated LCLo.

lethal concentration 50:

how much of a substance is needed to kill half
of a group of experimental organisms in a
given time.
a concentration of a pollutant or effluent at
which 50 per cent of the test organisms dies; a
common measure of acute toxicity
The concentration of a chemical in air or water
which is expected to cause death in 50% of
test animals living in that air or water

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
Absolute lethal concentration (LC100)-Lowest
concentration of a
substance in an environmental medium which
kills 100% of test organisms or species under
defined conditions

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The related quantities LD50/30 or an LD50/60

are used to refer to a dose that without
treatment will be lethal to 50% of the
population within (respectively) 30 or 60 days.
These measures are used more commonly
within Radiation Health Physics, as survival
beyond 60 days usually results in recovery.

LCt50,
which relates to lethal dosage from exposure, where C is
concentration and t is time.
It is often expressed in terms of mg-min/m. ICt50 is the dose that
will cause incapacitation rather than death.
These measures are commonly used to indicate the comparative
efficacy of chemical warfare agents, and dosages are typically
qualified by rates of breathing (e.g., resting = 10 l/min) for
inhalation, or degree of clothing for skin penetration.
The concept of Ct was first proposed by Fritz Haber and is
sometimes referred to as Haber's Law, which assumes that
exposure to 1 minute of 100 mg/m is equivalent to 10 minutes of
10 mg/m (1 100 = 100, as does 10 10 = 100).

For disease-causing organisms, there is also a measure

known as the median infective dose and dosage.
The median infective dose (ID50) is the number of
organisms received by a person or test animal qualified by
the route of administration (e.g., 1,200 org/man per oral).
Because of the difficulties in counting actual organisms in a
dose, infective doses may be expressed in terms of
biological assay, such as the number of LD50's to some test
animal.
In biological warfare infective dosage is the number of
infective doses per minute for a cubic meter (e.g., ICt50 is
100 medium doses - min/m).

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Limitation of LD50
factors such as the genetic
characteristics of the sample population,
animal species tested,
environmental factors
and mode of administration.
it measures acute toxicity only (as opposed to chronic
toxicity at lower doses), and does not take into account
toxic effects that do not result in death but are nonetheless
serious (e.g., brain damage).
There can be wide variability between species as well; what
is relatively safe for rats may very well be extremely toxic
for humans, and vice versa.

When used to test venom from venomous

creatures, such as snakes, LD50 results may be
misleading due to the physiological differences
between mice and humans.
Many venomous snakes are specialised predators
on mice; their venom may be adapted specifically
to incapacitate mice.
While most mammals have a very similar
physiology, LD50 results may or may not be
directly relevant to humans.