YY/T 0870.2-2019Test for genotoxicity of medical devices - Part 2: In vitro mammalian chromosome aberration test (English PDF)

Foreword

YY/T 0870 "Medical Toxicity Test for Medical Devices" consists of the following components.

--- Part 1. Bacterial back mutation test;

--- Part 2. In vitro mammalian cell chromosome aberration test;

--- Part 3. TK gene mutation test using mouse lymphoma cells;

--- Part 4. Mammalian bone marrow erythrocyte micronucleus test;

--- Part 5. Mammalian bone marrow chromosome aberration test. This part is the second part of YY/T 0870.

This part is drafted according to the rules given in GB/T 1.1-2009.

This part replaces YY/T 0870.2-2013 "Medical equipment genotoxicity test Part 2. In vitro mammalian cell chromosome aberrations Change test, compared with YY/T 0870.2-2013, except for editorial changes, the main technical changes are as follows.

--- Added terminology. aneuploidy (see 3.1); chromatid cleavage (see 3.2); chromatid cleft (see 3.3); chromosomal cleavage agent (see 3.6); mutation (see 3.8); p53 status (see 3.11); relative cell growth (see 3.12); relative population doubling (see 3.13); S9 liver homogenate (see 3.14); S9 mixture (see 3.15); untreated control (see 3.17);

--- Added a note to S9 (see Chapter 5);

--- Increased cell line selection (see Chapter 6);

--- Added notes on the preparation of sample preparation methods (see Chapter 8);

--- Increased the selection principle of positive controls (see 9.2);

--- Increased the evaluation method of cytotoxicity in the pre-experiment (see 10.1);

--- Added "laboratory capabilities" (see 10.6);

--- Added "historical comparison data" (see 10.7);

--- Increased the "acceptance criteria" (see 12.1);

--- Added "positive judgment criteria" (see 12.2.1);

--- Added "negative criteria" (see 12.2.2);

--- Added "interpretation of results" (see 12.2.3).

Introduction

The test methods for detecting potentially genotoxic substances given in GB/T 16886.3 are issued by the Organisation for Economic Co-operation and Development (OECD).

The methods specified in the Chemical Testing Guide, but these methods are developed for the characteristics of the chemical and no detailed test steps are given.

Therefore, it is not suitable for direct use in the detection of medical devices/materials. YY/T 0870 refers to the basic principles of the OECD test method, and according to the doctor The characteristics of the device/material have been modified as appropriate, and detailed test procedures have been specified, which can be used as GB/T 16886.3. Supplementary method criteria for genotoxicity testing.

This part of YY/T 0870 refers to the OECD 473 (2016) method and uses cultured cells with or without a metabolic activation system.

After the medical device/material is contacted, it is treated with a metaphase split phase blocker (such as colchicine or colchicine).

The chromosomal aberrations of mammalian cells in the mid-crack were analyzed to evaluate the potential for teratogenicity of the test samples.

The purpose of this section is to screen for substances in medical devices/materials that have the potential to cause chromosomal structural aberrations in mammalian cells.

There may be two types of chromosome structural aberrations, namely chromosomal type and chromatid type. For toxic chemicals contained in medical devices/materials In most cases, it induces chromatid aberrations, but sometimes it can also cause chromosomal aberrations. Polyploidy can occur in in vitro chromosome aberration test Increase in the number of (including intranuclear replication), polyploid itself does not indicate a strong potential to induce aneuploidy, only showing cell cycle interference Or cytotoxicity. However, this section does not apply to the detection of aneuploid mutagens and the aberrations of the number of chromosomes. This section needs to be used outside Source metabolic activation system. However, this exogenous system does not fully mimic the in vivo condition of mammals. Should pay attention to avoid by pH, seepage False positive results may result from changes in osmotic pressure or high levels of cytotoxicity.

This section uses established cell lines, primary cells of human or rodent origin. According to culture capacity, karyotype stability (including The number of chromosomes) and the frequency of chromosome aberration spontaneous selection experiments. Currently, although the available data cannot provide exact recommendations, However, when assessing chemical hazards, consider p53 status, genetic (karyotypic) stability, DNA repair capacity, and source (rodents and humans)

The choice is very important. Therefore, users of this section should consider these and other cell characteristics for cell lineage to detect chromosomal aberrations. The impact of energy. Medical device genotoxicity test Part 2. In vitro mammalian cell chromosome aberration test

1 Scope

This part of YY/T 0870 specifies test methods for chromosomal aberrations in mammalian cells in vitro for medical devices/materials.

This section applies to the evaluation of test samples by analyzing the chromosomal aberrations of animal cells in the middle of mitosis. Test method for potential teratogenicity.

Note 1. In vitro mammalian cell chromosome aberration test of oral materials is given in YY/T 0127.16.

Note 2. In vitro mammalian cell chromosomal aberration test of nanomaterials may require specific revisions to the methods in this section, but this section does not give description.

2 Normative references

The following documents are indispensable for the application of this document. For dated references, only dated versions apply to this document. For undated references, the latest edition (including all amendments) applies to this document.

GB/T 16886.1 Biological evaluation of medical devices - Part 1. Evaluation and testing in the process of risk management

GB/T 16886.3 Biological evaluation of medical devices - Part 3. Tests for genotoxicity, carcinogenicity and reproductive toxicity

GB/T 16886.12 Biological evaluation of medical devices - Part 12. Sample preparation and reference materials

3 Terms and definitions

The following terms and definitions as defined in GB/T 16886.1, GB/T 16886.3 and GB/T 16886.12 apply to this document.