GB/T 21759-2025Chemicals — Test method of chronic toxicity (English PDF)

3.1 adverse effects

Adverse changes in the morphology, physiology, growth, development, reproduction, or lifespan of an organism, system, or (sub)population.

Note. These changes can lead to impaired function, reduced ability to cope with additional stress, or increased sensitivity to other influences.

3.2 dose

The amount of test substance administered to laboratory animals.

Note. It is expressed in grams (g) or milligrams (mg), or in the mass of the test substance received by the experimental animal per unit body weight, such as mg/kg.

3.3 The lowest-observed-adverse-effect level (LOAEL)

The minimum effective dose of a test substance that causes adverse effects on the morphology, function, growth and development of experimental animals under specified conditions.

3.4 Chronic toxicity

Adverse effects resulting from ingestion, inhalation, skin contact or injection of a test substance after an exposure period of 12 months or longer.

3.5 Point of departure (POD)

The dose-response curve marks the starting point for low-dose extrapolation.

Note. This is usually the upper limit of the observed incidence rate or the incidence rate estimated by a dose-response model.

3.6

The specific way in which the test substance enters the organism.

Note. Examples include oral administration via gavage, oral administration via food, skin contact, inhalation, and intravenous injection.

3.7 No-observed-adverse-effect-level (NOAEL)

Compared to the control group, the test substance that did not cause any observable and statistically significant adverse effects in animals had the highest [performance/result]. Dosage level.

3.8 threshold

A specific dose or exposure level targeting a particular harmful effect.

Note. This effect will not be observed or expected when the level is below it.

4.1 General Principles

4.1.1 When assessing the toxicological properties of chemicals, laboratories should fully consider all available information about the test substance before testing to achieve more efficient results.

Assess its chronic toxicity potential while minimizing animal use. Information on the test substance to be considered includes. properties, chemical structure, and other relevant details.

Physicochemical properties, relevant information on toxic modes of action, results of any in vivo or in vitro toxicity tests, intended use, and potential human exposure.

(Q)SAR data and toxicological data of the substance, including its properties, structure, and related properties; available toxicokinetic data (including single-dose and repeated-dose kinetics).

Data from (e.g., repeated exposure studies) and other repeated exposure tests are required. Preliminary toxicity information is only available after repeated dose-toxicity studies at 28 and/or 90 days are conducted.

Only after this can chronic toxicity testing be conducted. Chronic toxicity testing employs a step-by-step testing method and is considered a potential health hazard of a specific chemical.

Part of the overall assessment.

4.1.2 Based on the experimental design and objectives, determine the most suitable statistical method for outcome analysis before the study begins. The following situations require special consideration.

Should the data on biological survival be adjusted and analyzed when one or more experiments are terminated early?

4.1.3 In repeated exposure studies, if animals exhibit progressive clinical symptoms and their condition continues to worsen, a decision should be made regarding whether to humanely euthanize the animal.

Make a wise decision. This decision is based on a trade-off between the value of the information obtained from the animal and its overall health. If the decision is to continue...

Increase the frequency of observation of the animal. Without affecting the experimental objectives, the administration of the poison can be temporarily stopped to alleviate the animal's pain or discomfort.

It's bitter, or you can reduce the dosage of the poison.

4.1.4 Dosage selection for chronic toxicity and carcinogenicity studies is based on the primary objective or purpose of the study. Dosage selection must consider the following two aspects.

The need for hazard screening; characterization of toxic effects at low doses and its practical significance. Low-dose toxicity is crucial when both chronic toxicity and carcinogenicity need to be studied simultaneously.

The toxic effects at certain doses are particularly important.

4.1.5 Where possible, combined trials of chronic toxicity and carcinogenicity should be prioritized over individual trials. Combined trials should consider both time and...

It is more cost-effective and does not affect data quality. When conducting combined trials, dosage selection principles must be carefully considered, while ensuring compliance with...

Requirements of the relevant management framework.

4.2 Experimental Principle

Laboratory animals are exposed to the test substance daily at a predetermined dose, typically for 12 months, but this period may be extended or shortened as required by regulations.

Exposure period. The exposure time should ensure that the cumulative toxic effect is significant, while avoiding interference with experimental results due to animal aging. If exposure occurs...

Any deviation from the 12-month exposure period (especially a shortened exposure period) must be clearly explained. Chronic toxicity tests are typically conducted orally.

The drug can be administered via inhalation or percutaneous route, but inhalation or percutaneous routes may also be chosen where applicable. The study design may include single or multiple necropsy procedures (e.g., in the third month).

(And in the 6th month), at which point the number of experimental animals needs to be increased. During the exposure period to the test substance, the animals should be closely monitored for toxic effects.

Animals that die or are euthanized during the experiment, as well as animals euthanized at the end of the experiment, must be dissected.