28-DAY REPEATED DOSE ORAL TOXICITY STUDY OF TEST FORMULATIONS IN RATS.
1.0
TEST SYSTEM DETAILS:
Species : Rattus norvegicus (Rats)
Age : 6-7
weeks
Sex : Male and Female
No. of animals : 10
(5M+5F) animals per group
Total animals : 60 (4 Extra) for 1 compound
2.0
ALLOCATION OF GROUPS:
|
Groups |
Treatment |
Dose;
ROA |
No. of animals |
Dose Volume |
|
Main Groups |
10 mL/kg |
|||
|
G1 |
Normal Control |
0.5% MC, p.o., q.d. |
5M+5F |
|
|
G2 |
Low Dose |
X1 mg/kg; p.o., q.d. |
5M+5F |
|
|
G3 |
Median Dose |
X2 mg/kg; p.o., q.d. |
5M+5F |
|
|
G4 |
High Dose |
X3 mg/kg; p.o., q.d. |
5M+5F |
|
|
Recovery Groups |
||||
|
G5 |
Normal Control |
0.5% MC, p.o., q.d. |
5M+5F |
|
|
G6 |
High Dose |
X3 mg/kg; p.o., q.d. |
5M+5F |
|
Abbreviations: MC-Methyl Cellulose, p.o.-per os; q.d.: quaque
die. The dose range will be from 100 mg/kg to 1000 mg/kg,
3.0
METHOD:
· The experiment will be conducted as
per OECD guideline number 407. The animals will be randomly allocated to 4 main
groups i.e., normal control, low, median & high dose, and 2 recovery groups
i.e., normal control and high dose group on the basis of their body weight.
Each group will be comprised of 5 male and 5 female animals. All animals will
be observed for any abnormal clinical signs prior to compound administration.
Post-randomization, animals will be acclimatized for 5 days in an experimental
room earmarked for the experiment.
· Animals of groups G1 and G5 will
receive 0.5% MC, p.o., q.d. for 28 days.
· Animals of groups G2, G3, G4, and G6
will receive test compounds at doses ranging from 100-1000 mg/kg, p.o., q.d. for
28 days.
· All animals will be observed daily
for mortality and clinical signs after initiation of compound administration.
Body weight, feed consumption, and detailed clinical examination will be
performed once a week. Main group animals will be observed for 28 days while
recovery group animals will be observed for an additional period of 14 days.
Functional observational battery assessments and ophthalmological examinations will be conducted during the 4th week for the main group animals and during the 6th week
for recovery group animals.
· After 28 days for the main group animals
and 42 days for the recovery group animals, a urinalysis will be performed and
animals will be sacrificed under an overdose of thiopentone. After suitable
anesthesia but before the animal dies, the blood sample will be collected from the retro-orbital route for estimation of hematological parameters and serum will
be separated by centrifugation for estimation of biochemical parameters.
Immediately after the animal dies, its organs will be harvested and collected
for histopathological analysis.
4.0
PARAMETERS TO BE EVALUATED:
· Clinical Signs
· Mortality
· Body Weight and feed consumption
· Ophthalmological examination
· Functional observational battery
· Urine analysis
· Hematology
· Serum biochemistry
· Absolute and relative organ weights
· Gross pathology
· Histopathology
5.0
REFERENCES:
1. Organization for Economic Co‐Operation and Development (OECD), “Test no. 407: repeated dose 28‐day oral toxicity study in rodents,”. OECD Guidelines for Testing of Chemicals, OECD, Paris, France (1995).
END OF THE DOCUMENT
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