Chinese Guidelines for the Testing of Chemicals - Health Effect

1. Revision Background

Chemical management requires that chemicals are assessed under a number of criteria and requiring the use of one or more experiments to provide data on physiochemical properties, hazards, effect on biotic systems, degradation and accumulation, health effect, etc. The test results serve as guidance for hazard evaluation, GHS classification and labeling, risk assessment and safety evaluation, as well as the risk management of chemicals.

The first edition of China’s “Guidelines for the Testing of Chemicals” (2004 edition) was published on May 2004, serving as the normative reference and core technical contents for the environmental standard “HJ/T 153-2004”. Drawing from the OECD guidelines for the testing of chemicals (prior to 2000) and relevant testing methods of USEPA and ISO, the first edition encompassed 90 testing items and 101 testing methods, of which 43 testing methods are for health effect. Counting up another 3 non-OECD testing methods, totally there are 46 testing methods for health toxicology included. The 3 non-OECD testing methods are plaque forming cell assay (PFC), delayed-type hypersensitivity test and natural killer cell activity assay.

Since 2010, Chemical management in China has shifted from hazard-oriented to the risk-oriented assessment with this paradigm shift mandating stricter requirements on standards of the test data produced. New testing methods and alternative methods are also constantly introduced to keep pace with the rapid advances in the art. To meet the management requirements and keep abreast with the international testing technology, the first edition of China’s “Guidelines for the Testing of Chemicals” was revised. 27 testing methods have been newly added in the revised guidelines which now totally cover 73 testing methods for health effect.

2. Introduction

“OECD guidelines for the testing of chemicals” is the world’s most comprehensive and widely-used system for chemical testing.30 years of use and refinement have made it the quintessential reference for development of sound chemical testing frameworks worldwide. The revision to the first edition of China’s “Guidelines for the Testing of Chemicals” was made by primarily referring to the 2012 version of the OECD guidelines in terms of health toxicology and appropriately referring to other advanced methods.

The testing methods adopted from OECD guidelines still follow the OECD testing No., such as test No. 401 “Acute Oral Toxicity”, test No. 402 “Acute Dermal Toxicity”. The date the testing method was published or the latest date of revision will be indicated in the reference part to facilitate search and comparison. The revision to the first edition is to include the OECD testing methods published by the end of 2012, thus Chinese labs should follow suit and adhere to the technical requirements and standards outlined in OECD testing system (2012).

Additionally 4 non-OECD testing methods are adopted which lack a Test No:

Macrophage phagocytic function test”
Embryotoxicity testing in post-implementation whole embryo culture,
WEC test”, “Micromass test, MM test”
Embryonic stem cell test, EST”.

The guidelines were revised in accordance with the 3Rs principles (Replacement, Refinement and Reduction) and to factor in global trends towards replacement of animal testing with more ethical alternatives. An excellent example of where China deviates from unilateral implementation of OECD guidelines is seen in China’s continued use of the now redundant OECD test No. 401 (Acute Oral Toxicity test). Although deleted from the revised OECD guidelines it is still used extensively in China. China’s labs can exercise some discretion in their choice of test when assessing acute oral toxicity. Choice is available between the traditional 401 test and OECD updates such as:

No. 420 “Acute Oral Toxicity - Fixed Dose Procedure” (2001)
No. 423 “Acute Oral toxicity - Acute Toxic Class Method” (2001)
No. 425 “Acute Oral Toxicity: Up-and-Down Procedure” (2008),

The revision to the Chinese testing guidelines specifically those assessing health effect, has encompassed many of the OECD principles while still being tailored to cater to the resources and facilities available to Chinese laboratories.

In China’s new “Guidelines for the Testing of Chemicals” each testing method, including the appendix will also clearly indicate the editorial staff involved in the revisions or additions to the guidelines. Revision to the first edition will be indicated as “XX edit” (where XX indicates the name of the editor). Newly introduced items updated from the 2004 edition should be indicated as “XX compile” (where XX indicates the name of the editor).

The revised guidelines will be basis for testing institutions to carry out chemical testing. In fact due to the wide variety of chemicals requiring testing, none of the testing methods can fully assess a chemical under all the necessary criteria. Thus, laboratories should reference the testing methods provided in the guidelines and design testing protocols according to their own lab conditions and specifics of the test item.

3. Testing Methods

For the part of health effect in the first edition of “Guidelines for the Testing of Chemicals” (2004 version), 21 OECD testing methods are updated to their advanced version.

Table 1. Testing Methods updated in the revised edition of China’s guidelines

Serial No.	Testing Method in China’s Guidelines for the Testing of Chemicals”	The version of OECD testing methods adopted in the first edition of China’s guidelines (2004 version)	The version of OECD testing methods adopted in the revised edition of China’s guidelines (2013 version)
1.	403 Acute Inhalation Toxicity Test	1981	2009
2.	404 Acute Dermal Irritation/Corrosion Test	1992	2002
3.	405 Acute Eye Irritation/Corrosion Test	1987	2012
4.	407 Repeated Dose 28-day Oral Toxicity Study in Rodents	1995	2008
5.	408 Repeated Dose 90-Day Oral Toxicity Study in Rodents	1981	1998
6.	409 Repeated Dose 90-Day Oral Toxicity Study in Non-Rodents	1981	1998
7.	412 Subacute Inhalation Toxicity: 28-Day Study	1981	2009
8.	413 Subchronic Inhalation Toxicity: 90-day Study	1981	2009
9.	414 Prenatal Developmental Toxicity Study	1981	2001
10.	416 Two-Generation Reproduction Toxicity	1983	2001
11.	417 Toxicokinetics	1984	2010
12.	420 Acute Oral Toxicity - Fixed Dose Method	1992	2001
13.	423 Acute Oral Toxicity - Acute Toxic Class Method	1996	2001
14.	425 Acute Oral Toxicity: Up and Down Procedure	1998	2008
15.	451 Carcinogenicity Studies	1981	2009
16.	452 Chronic Toxicity Studies	1981	2009
17.	453 Combined Chronic Toxicity/Carcinogenicity Studies	1981	2009
18.	473 In vitro Mammalian Chromosome Aberration Test	1983	1997
19.	474 Mammalian Erythrocyte Micronucleus Test	1983	1997
20.	475 Mammalian Bone Marrow Chromosome Aberration Test	1984	1997
21.	476 In vitro Mammalian Cell Gene Mutation Test	1984	1997

Compared with the first edition of “Guidelines for the Testing of Chemicals” (2004 version), 27 new testing methods are added in the revised guidelines (2013 version). Table 2. Testing Methods Newly Added into the Health Effect Part of the Revised Guidelines (2013 Version)

Serial No.	Testing Method in China’s Guidelines for the Testing of Chemicals”	The version of OECD testing methods newly adopted in the revised edition of China’s guidelines (2013 version)
1.	426 Developmental Neurotoxicity Study	2007
2.	427 Skin Absorption: in vivo Method	2004
3.	428 Skin Absorption: in vitro Method	2004
4.	429 Skin Sensitisation	2010
5.	430 In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test, TER	2013
6.	431 In Vitro Skin Corrosion: Human Skin Model Test	2013
7.	432 In Vitro 3T3 NRU Phototoxicity Test	2004
8.	435 In Vitro Membrane Barrier Test Method for Skin Corrosion	2006
9.	436 Acute Inhalation Toxicity Test: Acute Toxic Class Method	2009
10.	437 Bovine Corneal Opacity and Permeability Test, BCOP	2013
11.	438 Isolated Chicken Eye Test, ICE	2013
12.	439 In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method	2013
13.	440 Uterotrophic Bioassay in Rodents: A Short-term Screening Test for Oestrogenic Properties	2007
14.	441 Hershberger Bioassay in Rats: A Short-term Screening Assay for (Anti) Androgenic Properties	2009
15.	442A Local Lymph Node Assay - DA	2010
16.	442B Local Lymph Node Assay – BrdU-ELISA	2010
17.	443 Extended One-Generation Reproductive Toxicity Study	2012
18.	455 Performance-Based Test Guideline for Stably Transfected Transactivation In Vivo Assays to Detect Estrogen Receptor Agonists	2012
19.	456 H295R Steroidogenesis Assay	2011
20.	457 BG1Luc Estrogen Receptor Transactivation Test Method for Identifying Estrogen Receptor Agonists and Antagonists	2012
21.	460 Fluorescein Leakage Test Method for Identifying Ocular Corrosives and Severe Irritants	2012
22.	487 In Vitro Mammalian Cell Micronucleus Test	2010
23.	488 Transgenic Rodent Somatic and Germ Cell Gene Mutation Assays	2013
24.	Macrophage Phagocytic Function Test	——
25.	Embryotoxicity Testing in Post-Implementation Whole Embryo Culture, WEC Test	——
26.	The Micromass Test, MM Test	——
27.	Embryonic Stem Cell Test, EST	——

About the Author

Mr Jim Wei is the CEO and co-founder of the REACH24H Consulting Group. Mr Wei has worked as the official in the Safety Test Laboratory of Zhejiang Inspection & Quarantine Bureau (CIQ) for 9 years. As one of the experts of EU REACH compliance WG of AQSIQ China, Mr Wei has many expereicnes on EU REACH regualtion project.

English version of this article is contributed by Nadine He.