The abnormal toxicity test method is a method of detecting the toxicity of a chemical substance, which is determined by observing the abnormal reaction of experimental animals after exposure to or ingestion of toxic substances. The basic principle of this method is to use the sensitivity of experimental animals to poisons, and judge the toxicity of substances by observing the abnormal behavior, physiological indicators and pathological changes of animals.
Abnormal toxicity testing methods are usually conducted using two experimental methods: acute toxicity tests and chronic toxicity tests. Acute toxicity test is to give experimental animals one or more exposures to a substance in a short period of time to observe its acute toxicity; The chronic toxicity test is to continuously expose experimental animals to a certain substance for a long time to observe their chronic toxicity.
Purpose and principle of the test:
Abnormal toxicity is different from the toxicity profile of the drug itself, and refers to toxicity caused by introduction or other causes during the manufacturing process.
This method is to give animals a certain dose of test solution, observe the abnormal reaction or death of the animal within the specified time, check whether the test sample is contaminated with exogenous toxic substances and whether there are unexpected unsafe factors, the preparation of the test solution is made according to the concentration specified under the variety.
Requirements for the test:
Before use, the test solution should be balanced to room temperature. The test animals should be healthy and qualified, and should be raised according to normal feeding conditions before the test and during the observation period of the test. Animals that have had this test should not be reused.
Non-biological product trials:
Unless otherwise specified, 5 mice weighing 18 22g were taken, and each mouse was given intravenous test solution 05ml, which should be injected at a constant rate within 4 to 5 seconds. Varieties that prescribe slow injections can be extended to 30 seconds. Unless otherwise specified, all mice must not die within 48 hours of dosing; In case of death, 10 mice weighing 19 21g should be taken for retest, and all mice should not die within 48 hours.
Biologics Trials:
Unless otherwise specified, the abnormal toxicity test should include the mouse test and the guinea pig test, and the test should be set up with a blank control of the same batch of animals, during the observation period, all the animals are alive and there is no abnormal reaction, and the weight of each animal should increase when it expires, then the test is judged to be valid. Slowly injected into the animal according to the prescribed route of administration.
Mouse Test:
1) Unless otherwise specified in the mouse test method, 5 mice were taken, and each mouse was weighed before injection, which should be 18 22g. Each mouse is intraperitoneally injected with test solution 05 ml, observe for 7 days. During the observation period, all mice should be alive and healthy, and there should be no abnormal reactions, and the weight of each mouse should increase at the expiration of the period to determine that the test products meet the requirements. If the above requirements are not met, 10 mice weighing 19 21g should be taken for retest, and the judgment criteria are the same as before.
2) Unless otherwise specified, 2 guinea pigs should be taken, and each mouse should be weighed before injection, which should be 250 350g. Each guinea pig is intraperitoneally injected with test solution 50ml, observed for 7 days. During the observation period, all guinea pigs should be alive and healthy, and there should be no abnormal reactions, and the weight of each guinea pig should increase at the expiration of the period to determine that the test product meets the requirements. If the above requirements are not met, 4 guinea pigs can be used to retest once, and the judgment criteria are the same as before.