LONG-TERM (AT LEAST 24 MONTHS)
TOXICITY
PURPOSE:
A broad screen for toxicity that will define effects, establish the NOEL, and determine carcinogenicity
ANIMALS:
Rodents-50/sex/group with increases for sacrifices planned before the end of the test.
Dogs-8/sex/group
DOSAGE:
At least three plus control.
Lowest dose should not show toxicity.
At least 50% of the animals should survive for 24 months.
The highest dose is usually the highest amount that can be administered without reducing the life span of the animals unless that dose exceeds 5% of the diet.
OBSERVATIONS:
Daily observations similar to sub-chronic studies.
Histopathology to include:
Adrenal |
Peripheral Nerve |
|
Aorta |
Pituitary |
|
Bone |
Prostate |
|
Bone Marrow |
Rectum |
|
Brain (3+Levels) |
Rep. Lymph Nodes |
|
Caecum |
Salivary Glands |
|
Colon |
Seminal Vesicle |
|
Corpus & Cervis Uteri |
Skeletal Muscle |
|
Duodenum |
Smooth Muscle |
|
Esophagus |
SpinalCord (2+Levels) |
|
Eyes |
Spleen |
|
Gall Bladder |
Sternum |
|
Heart |
Stomach |
|
Ileum |
Testes |
|
Jejunum |
Thymus |
|
Kidneys |
Thyroid (Parathyroid) |
|
Liver |
Trachea |
|
Lungs |
Urinary Bladder |
|
Mammery Glands |
All tissues showing abnormality |
|
Ovaries |
||
Pancreas |
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