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Lecture of week 12
If the drug shows serious adverse effects, FDA has its authority to
RECALL the drug from the market.
1. Animal species:
At least 2 species are required
Rats and mice are usually used, but sometimes dogs and rabbits are
also included.
3. Route of administration:
The chemical should be administered by the same route with which
human would be administered. (e,g: Oral gavage, Ocular, Dermal,
Intraperitoneal, lnhalation, intravenous, Intramuscular, Intranasal,
Subcutaneous)
Sometimes, we use more than two route of administration to assess
potential hazardous effects of chemical handling by human.
e.g: if the route of human exposure would be oral, acute dermal, eye,
and inhalation studies may be indicated to assess the hazard to
personnel's handling the compound.
4. Dosing :
single dose or multiple doses
5. Animal Monitoring:
The animals are observed for 14 days after chemical administration.
Observations include:
A. Inhalation test
It is used for assessment of the toxic hazard of agents whose
principal route of exposure is via inhalation and to Study of the
comparative toxicity of agents administered by different routes.
LC50 (median lethal concentration) is the parameter of choice of
this test. (where C = concentration of inhaled chemicals for a
fixed time T
Comparative LC50 data are often obtained for 4-hrs exposures
and a 14-day post-exposure observation period.
The most species used for inhalation studies include rats, dogs,
and monkeys.
B. Draize test
It is an acute toxicity tests that initially used for testing of topical
preparations.
It includes:
1. Ocular test
In this test, conscious rabbits are immobilized while chemicals are put
directly into their eyes. They are often left for as long as a week.
Injuries to the eyes after the exposure are determined by an irritancy
value (score). After the test, the rabbits are usually killed and internal
effects on the rabbits are examined.
2. Dermal irritation test
Skin corrosion and dermal irritation tests are typically conducted by
placing a chemical or chemical mixture on the skins of animals, usually
rabbits.
1. Animal species:
At least 2 species are required, one rodent and one nonrodent.
Rats and dog are usually used (because of their availability &
complete physiological background of these species).
These tests should be done during the period of the most rapid
growth of the animal. (e.g: just after weaning of rats)
3. Route of administration:
The chemical should be administered by the same route with
which human would be administered.
5. Animal Monitoring :
The animals are observed at 3-week intervals during exposure and
last up to 3 months following termination of exposure.
Parameters to be tested include:
A. Animal weights
B. Daily Food and water consumption
C. Biochemical organ function tests
D. Metabolic studies
E. Hematologic studies
F. Postmortem examination
These parameters are statistically compared to those obtained
from control groups of animal.
Control groups include Negative control and vehicle received
control.
Metabolic studies
The toxic nature of the metabolites and the rate of metabolic
transformation of the test compound are of essential parameters t
be evaluated in this toxicity studies.
Urine and faeces can be collected and examined for the presence
of metabolites.
Postmortem examination
All animals should be subjected to autopsy that include gross and
histopathological examination of all organs.
1. Animal species:
A wide variety of animal species should be used in this type of work.
At least 2 animal species are required, these include:
A.Rodents are the animals of choice, since large numbers can be
used to aid in the statistical interpretation of the results.
B.Dogs and monkey (Larger animals) should also be used for such
species have the advantage that larger samples of blood can be
obtained on a routine basis.
N.B: for studying of the carcinogenic potential of a compound, the
rat, mouse, or hamster is usually chosen because of its:
Shorter lifetime.
Ability of using large numbers (to increase the sensitivity of the
test).
3. Route of administration:
The chemical should be administered by the same route with
which human would be administered.
N.B: For food additives, pesticides, and other chemicals likely to
come into contact with food or water, it is recommended to
incorporate the test chemical into the diet or drinking water.
4. Dosing :
Selection of doses for chronic studies obtained from the results
of subchronic toxicity studies.
At least 2 dose levels required.
5. Animal Monitoring :
The same as subchronic toxicity studies.
Assignment
Assignment
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