REGULATORY ASPECTS OF COSMETIC PRODUCT TESTING AND THE ROLE OF ALTERNATIVE MODELS IN MODERN STRATEGIES

Abstract

Modern regulatory frameworks in the field of cosmetic products increasingly promote the use of alternative methodologies (New Approach Methodologies, NAMs) based on in vitro, ex vivo, and in silico approaches, accompanied by strict limitations or complete bans on animal testing. In such a regulatory environment, interest is growing in models capable of bridging the gap between cellular systems and complex in vivo studies. Zebrafish (Danio rerio) embryos have been recognized as a potential bridging model due to their high biological relevance, testing versatility, and the more favorable ethical status of early developmental stages. This paper provides a systematized overview of regulatory frameworks in the EU, the USA, Asia, and Serbia, highlighting the degree of acceptance of alternative methods and the specific status of zebrafish in the context of the safety assessment of cosmetic products and ingredients. It analyzes the scientific advantages and limitations of the zebrafish model, including genetic similarity to humans, embryonic transparency, and rapid development, as well as limitations that restrict its use as primary evidence in regulatory documentation. The comparative analysis indicates that zebrafish are most appropriately used as a supplementary source of data within weight-of-evidence and NAM-oriented strategies, particularly in early-stage hazard screening and the mechanistic understanding of the effects of new bioactive substances. In line with international trends and the harmonization of the national regulatory framework with EU requirements, the findings suggest that zebrafish embryos represent a valuable research and development tool, but not a substitute for validated methods that form the basis of regulatory safety assessment of cosmetic products.