Development in Alternatives to Animal Testing of Cosmetics in China

Takehome:

• China has already approved two alternatives testing methods to animal testing to assess skin sensitivity and eye irritation. An additional four alternatives testing methods are currently undergoing public feedback and two more are currently in the research and development phase.
• On Sep 19, 2018, China Working Group for the Validation of Alternative Testing Methods was newly established.

On Sep 20-21, 2018, the 2nd International Conference on Cosmetics Alternative Testing Methods was hosted by NIFDC. The conference invited the ECVAM, JaCVAM, PCPC, JCIA, IIVS, Tissue Engineer R&D Center of the Fourth Military Medical University, Guangdong CDC and cosmetics industry experts to give lectures focusing on three topics: 

1. Alternative methods policies
2. Cosmetic safety evaluation and risk assessment
3. Validation of alternative methods

Latest Developments in Alternative Testing Methods in China

On Nov 11, 2016, China included 3T3 NRU Phototoxicity Test as a toxicology test method into Safety and Technical Standards for Cosmetics. Then on Aug 15, 2017, Skin Corrosion: Transcutaneous Electrical Resistance Test was accepted as in vitro test method for skin corrosion.

On Feb 5, 2018, China opened public consultation on 2 new draft standards for 2 additional alternative testing methods to public consultation namely:

1.  Skin Sensitivity: Direct Peptide Reactivity Assay
2.  Eye Irritation(Corrosion): Short Time Exposure

On Jun 27, 2018, China opened public consultation on 2 new draft standards for two more alternative testing methods namely:

1. Skin Sensitivity: Murine Local Lymph Node Assay: DA
2. Skin Sensitivity: Local Lymph Node Assay: BrdU-ELISA

Currently, Eye Irritation (corrosion): Porcine Corneal Opacity Permeability and Genotoxicity: In Vitro Micronucleus are under research. The research on Eye Irritation (corrosion): Fluorescent Leakage test and Skin Sensitivity: 442E(h-CLAT), 442D will commence soon.

China Working Group for the Validation of Alternative Methods

On Sep 19, 2018, China Working Group for the Validation of Alternative Methods was newly established. This working group is organized by NIFDC and covers 15 units including cosmetics testing institutions, scientific research institutions and representatives of the cosmetics industry.

The working group’s major goal is to improve the validation and utilization of alternative testing methods which can act as viable surrogate markers in the assessment of potential toxicities, adverse effects and hazards of cosmetics and ultimately reduce China’s reliance on the use of animal testing. Feasibility criteria are based on the inherent characteristics of China’s cosmetic industry, consumers and product lifecycle.

Although China has not yet established a Center for the Validation of Alternative Methods, the establishment of the working group is also a major step forward.

Industry Standards Issued by China' s Regulatory Authorities for Cosmetic Alternatives for Animal Testing (to be continued)

The Problems & Challenges Facing China in AAT Validation

OECD Guidelines for the Testing of Chemicals is a collection of about 180 of the most relevant internationally agreed testing methods used by government, industry and independent laboratories to identify and characterize potential hazards of chemicals. These methods include toxicological tests such as skin corrosion, skin irritation, eye irritation, skin sensitization, phototoxicity test, etc.

Although the alternatives in OECD Guidelines have been able to evaluate cosmetic ingredients and formulation safety, it is still impossible to obtain reliable data only from alternatives in terms of systemic toxicity testing (genotoxicity, carcinogenicity, embryo toxicity, etc.), especially for subchronic and long-term toxicity evaluation.

Since 2011, China NIFDC has initiated the research and validation of alternatives for animal testing with reference to OECD guidelines. In 2016 and 2017, two alternative methods were included into Safety and Technical Standards for Cosmetics. However, due to the late start of AAT validation, there are still some problems and challenges facing China.

1. The Applicability & Feasibility

• In the OECD testing guidelines, the test target is "chemical (including mixtures)", and does not align with China' s definition of cosmetics. A lot of cosmetic products or botanical ingredients are not suitable for in vitro assessment, e.g. wax, cream, colorful compounds, plant ingredients with unknown concentration.
• Of the 8783 kinds of cosmetic ingredients in China' s IECIC, 30% of them are animal and plant extractions. Botanicals present challenges in safety assessment as complex mixtures derived from a large and diverse class of materials includes extracts, hydrolysates, juices, powders, resins, saps, tars and seedcakes. Colored substances in the ingredients can impact testing. Currently it is still unknown whether botanical substances are suitable to be tested by alternative methods.
• Validation and verification is requires more than a simple translation of the protocol, it should be suitable for Chinese conditions. Take Eye Irritation: BCOP as an example. Compared to pigs, cattle are rarely bred in China, the acquisition of bovine cornea is limited by the cost. Pigs are common in China, Porcine Corneal Opacity and Permeability is more suitable for Chinese conditions.

2. The Accessibility of Materials

• There are some problems on importing the specific cell lines, tissue models and establishing facilities of adequate technical capacity. The strong method patent protection and special testing facilities will both increase the cost of testing and affect the promotion of alternative methods in China.
• Among the alternative methods in OECD guidelines, there are 4 types of approved skin models and 2 types of corneal models. The IP is owned by overseas enterprise, only one type of reconstructed human models (skin and corneal) can be produced and purchased in China. In vitro reconstructed human models are biologically active, the transportation and importation will affect the activity of the model, thus affecting the test results.
• Domestic models are hardly validated and accepted worldwide.

3. Industry Technical Capacity Shortcomings Hindering Greater AAT Traction

Cosmetic safety assessment requires sufficient technical capacity. For the most part China' s cosmetic industry is fragmented and market share divided amongst small and medium enterprises with relatively weak technical capacity. As such China' s government must take a major role in assuring product quality and safety assurance. In the short term a total ban on animal testing is unlikely given the lack of testing infrastructure and the technical capacity shortcomings of the industry. As investment increases more competitive domestic enterprise emerge and when combined with increased awareness of ethical concerns at a consumer level we can expect China to eventually realize a cruelty free cosmetic sector.