GB 15193.1-2014 English PDF (GB15193.1-2014)
GB 15193.1-2014 English PDF (GB15193.1-2014)
GB 15193.1-2014: National Food Safety Standard -- Procedures for toxicological assessment of food
NATIONAL STANDARD OF THE
PEOPLE REPUBLIC OF CHINA
National food safety standard ?€?
Procedures for toxicological assessment of food
ISSUED ON. DECEMBER 24, 2014
IMPLEMENTED ON. MAY 01, 2015
Issued by. National Health and Family Planning Commission of the PRC
Table of Contents
Foreword ... 3
1. Scope ... 4
2. Requirements for test substances ... 4
3. Contents of toxicological assessment for food safety ... 4
4. Principle of selecting toxicity test for different test substances ... 5 5. Objective of toxicological assessment of food and result judgment ... 8 6. Factors that need to be considered during food safety assessment .. 11 Procedures for toxicological assessment of food
This Standard specifies the procedure for toxicological assessment of food. This Standard is applicable to the assessment of the safety of chemical, biological and physical factors that may cause harm to health concerned during food production, processing, storing, transport and selling process. Assessment objects include food and its raw material, food additives, new food raw materials, irradiated food, food related products (used for food packaging materials, containers, detergent, disinfectant; and the tools and equipment used for food production and marketing), and food pollutants. 2. Requirements for test substances
2.1 It shall provide the test substance?€?s name, batch number, content, storage conditions, sources of raw materials, production processes, quality specifications, character, human recommended (possible) intake, and other relevant information. 2.2 For single-ingredient chemical substance, the physical, chemical property (including chemical structure, purity, stability, etc.) of test substance (including impurities when necessary) shall be provided. For mixed substances (including formulated products), the composition of test substance shall be provided; when necessary, physical property, chemical property (including chemical name, structure, purity, stability, solubility, etc.) of all compositions of test substances and relevant data shall be provided.
2.3 If the test substance is formulated product, it shall be the standardized product; its composition ingredients, proportion and purity shall be the same as the actual application. If the test substance is an enzyme preparation, it shall, before other compound ingredients are added, use the product as the test substance.
3. Contents of toxicological assessment for food safety
3.1 Acute oral toxicity test.
3.2 Genetic toxicity test.
3.2.1 Genetic toxicity test contents. Bacterial reverse mutation test, mammalian erythrocyte micronucleus test, mammalian bone marrow chromosome aberration test, mouse spermatogonia or spermatocytes chromosome aberration test, in-vitro mammalian cell HGPRT gene mutation test, in-vitro mammalian cell TK gene mutation test, in-vitro carcinogenicity studies (or chronic toxicity and carcinogenicity merge test). 4.2 For derivatives or analogs of which the chemical structure is basically same as that of known substances (refer to those that have passed safety evaluation and are allowed for use), or the substances that have safe-use history in some countries and regions, then it may firstly conduct the acute oral toxicity studies, genetic toxicity test, 90-day oral toxicity test, and teratogenicity test. According to the test results, determine whether it needs to conduct the toxicokinetic test, reproductive toxicity test, chronic toxicity test and carcinogenicity test, etc.
4.3 For substances that are known or have use history in several countries, at the same time, the application organization has the data to prove that the quality specifications of the declared test substance are consistent with foreign products, then it may firstly conduct the acute oral toxicity test, genetic toxicity test, and 28-day oral toxicity test. According to the test results, determine whether it needs to further conduct toxicity test. 4.4 Selection of the safety toxicology assessment test for food additives, new resources of food and ingredients, food related products, pesticide residue, veterinary drug residue
4.4.1 Food additives
184.108.40.206.1 All the flavorings that have been approved for use or have been formulated for daily acceptable intake by World Health Organization (WHO), and allowed by two or more organizations of WHO, FEMA, COE and IOFI, then it generally is not required to conduct test.
220.127.116.11.2 If the data is incomplete or is only approved by one of the international organizations, then acute toxicity test and one of genetic toxicity test combination shall be conducted first; decide whether further test is needed after preliminary assessment. 18.104.22.168.3 If no data can be referred to and it is not yet allowed to use by international organization, then conduct the acute toxicity test first, genetic toxicity test and 28-day oral toxicity test. decide whether further test is needed after preliminary assessment. 22.214.171.124.4 For single high-purity natural flavoring that is extracted from edible part of animal or plant, if the chemical structure and relevant data do not show un-safety, then toxicity test is generally not required.
126.96.36.199 Enzyme preparations
188.8.131.52.1 For enzyme preparations that have long history of safe consumption and that are produced from edible parts of animals or plants, if the World Health Organization has announced the acceptable daily intake (ADI) or ADI is not required to be specified or several countries have approved the use, on the basis of providing relevant proving 4.4.2 New food raw materials
It shall be evaluated in accordance with "New food raw material declaration and acceptance provisions" (State-Health-Food-Announcement  23).
4.4.3 Food related products
It shall be evaluated in accordance with "Food related product new varieties declaration and acceptance provisions" (Health-Supervision-Announcement  49). 4.4.4 Pesticide residue
It shall be evaluated in accordance with GB15670.
4.4.5 Veterinary drug residue
It shall be evaluated in accordance with "Veterinary drug before-clinical toxicology evaluation test guidelines" (The People's Republic of China, Ministry of Agriculture Bulletin No. 1247).
5. Objective of toxicological assessment of food and result
5.1 Objectives of toxicological test
5.1.1 Acute toxicity test
Understand the degree of toxicity, property and possible target organ of test substance; provide basis for selection of dose and toxicity observation index for further toxicity test; classify the acute toxicity dosage according to LD50.
5.1.2 Genetic toxicity test
Screen the genetic toxicity of test substance and whether it has potential carcinogenesis and cell mutagenicity.
5.1.3 28-day oral toxicity test
On the basis of the acute toxicity test, understand more about the nature of the test substance?€?s toxicity, the dose-response relationship and possible target organs, so as to obtain the 28-day oral not-observed adverse effect dose; preliminarily evaluate the safety of the test substance; and provide the basis for selecting longer-term toxicity and chronic toxicity test dose, observation indicators, toxicity endpoint for next step. 5.1.4 90-day oral toxicity test
alternative tests (at least one is in-vivo test). If the additional 2 alternative tests are negative, it may proceed to the next toxicity test; if 1 item is positive, it shall give up that the test substance can be used in food.
184.108.40.206 If all 3 items are negative, then it may proceed to the next toxicity test. 5.2.3 28-day oral toxicity test
For test substances that only require to conduct acute toxicity, genetic toxicity and 28-day oral toxicity test, if the test is found without significant toxic effects, the preliminary assessment may be made on considering other various test results. If the test is found to have significant toxicity, especially when there is dose-response relationship, then it shall consider to conduct further toxicity test.
5.2.4 90-day oral toxicity test
According to the not-observed adverse effect dose obtained by the test to conduct assessment, the principle is.
a) If not-observed adverse effect dose is less than or equal to 100 times of recommended (possible) human-intake, it indicates stronger toxicity; it shall give up that the test substance can be used in food;
b) If not-observed adverse effect dose is more than 100 times but less than 300 times, it shall conduct chronic toxicity test;
c) If not-observed adverse effect dose is more than or equal to 300 times, then chronic toxicity test is not required; it may proceed to safety assessment.
5.2.5 Teratogenicity test
According to the test results, evaluate if the test substance is the teratogenic substance to laboratory animals. If teratogenic test result is positive, then reproductive toxicity and reproductive-developmental toxicity test shall not be continued. For other developmental toxicities that are observed in teratogenicity test, it shall combine with 28-day and (or) 90-day oral toxicity test results to conduct the assessment.
5.2.6 Reproductive toxicity test and reproductive-developmental toxicity test According to the not-observed adverse effect dose obtained by the test to conduct assessment, the principle is.
a) If not-observed adverse effect dose is less than or equal to 100 times of recommended (...