Professional Documents
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Margin of Safety
= LD1 / ED99
Therapeutic Index
Margin of Safety
Potency and Efficacy
Potency – Is given by the position of
the dose-response curve along the x-
axis; farther to the left = more potent
Efficacy – Is given by the peak of the
dose-response curve; the higher the
peak the greater the maximum effect or
efficacy
Potency and Efficacy
Carcinogenic Chemical Dose-
Response Graph
Tumors Graph
Tumors
Ames Test For Mutagenicity
Assumption – Any substance that is
mutagenic for the bacteria used in the
test may also turn out to be a
carcinogen.
Benefits of Test – Easy to conduct, low
cost
Drawbacks – Test gives some false
negatives and some false positives
Ames Test - Continued
Test strain of bacterium used is a strain
of Salmonella typhimurium that carries
a mutant gene making it unable to
synthesize the amino acid histidine from
ingredients in its culture
A “back mutation” to this gene will allow
the hisidine requiring strain of bacteria to
grow on histidine deficient media.
Ames Test - Continued
The test involves placing the histidine-
requiring strain of bacteria on a culture
plate along with the test chemical. If
the bacteria grow on the histidine-
deficient culture medium, a mutation
has occurred
Therefore, the test chemical is mutagenic
and possibly carcinogenic
Effects of More Than One
Chemical
Additive Effect: the combined effect of the
two chemicals is equal to the sum of the
effects of each agent given alone. This is the
most commonly observed effect when two
chemicals are given together. (2 + 2 = 4)
Effects of More Than One
Chemical – Continued
Synergistic Effect: occurs when the
combined effects of two chemicals are much
greater than the sum of the effects of each
agent given alone.
CCl4 and ethanol are hepatotoxic alone but when
given together produce much more liver injury than
the mathematical sum of their individual effects. (2
+ 2 = 20).
Smoking and asbestos exposure is another example.
Cocaine use with alcohol use is a third example.
Cocaine + Alcohol
Metabolism of ethanol and cocaine
together produces a metabolite called
cocaethylene. This metabolite of
cocaine and ethanol has
pharmacological properties similar to
those of cocaine but with a longer
duration in the blood plasma (three to
five times as long).
Effects of More Than One
Chemical – Continued
Potentiation: occurs when one
compound does not have a toxic effect
on a certain organ or system but when
added to another chemical makes that
chemical much more toxic.
CCl4 is hepatotoxic, isopropanol is not
hepatotoxic, when given together the effect
of CCl4 is more than expected. (0 + 2 = 10)
Effects of More Than One
Chemical – Continued
Antagonism: occurs when two
chemicals administered together
interfere with each other’s action.
Antagonistic interactions are very often
desirable in toxicology and are the basis
of many antidotes. (2 + (-2) = 0).
Types of Antagonism
Functional antagonism occurs when two
chemicals counterbalance each other by
producing opposite effects on the same
physiological function.