Ement, Reduction and Refinement (i.e., Three Rs1) of animal testing. Additionally, Reach (2020g) along with the Cosmetic Merchandise Regulation (2020e) have either contributed to the implementation from the 3Rs by, respectively referring to and encouraging the useThree Rs and 3Rs are made use of interchangeably.Vol.:(0123456789)Archives of Toxicology (2021) 95:1867of alternatives to animal testing, or banning animal testing altogether. Along this line, for some certain toxicological endpoints (e.g., skin corrosion and irritation, significant eye damage and irritation, skin sensitisation, and mutagenicity and genotoxicity), the prospective hazard of chemicals is often evaluated using non-animal approaches. Nevertheless, for other endpoints, for example acute systemic toxicity, repeated dose toxicity and reproductive and developmental toxicity, the regulatory needs, and as a result chemical security evaluation, nevertheless heavily KDM5 Biological Activity relies around the use of animals. D5 Receptor Biological Activity understanding current regulatory requirements specific for the assessment of chemical and cosmetic ingredient effects on human health is crucial to recognize attainable understanding gaps, and evaluate how alternative (non-animal) methods could possibly be integrated in existing regulatory practice. This is in line with recent initiatives taken by the International Cooperation on Alternative Test Solutions (ICATM) (https://ec.europa.eu/jrc/en/eurl/ecvam/alter native- metho ds- toxic ity- testi ng/ advis ory- bodies/ icatm), whose members consist of EURL ECVAM (European Union Reference Laboratory for Options to Animal Testing) with the European Commission’s Joint Research Centre (JRC), ICCVAM (the US Interagency Coordinating Committee on the Validation of Option Techniques) in the National Institute of Environmental Health Sciences, JaCVAM (Japanese Center for the Validation of Option Solutions) at the National Institute of Overall health Sciences, Health Canada, and KoCVAM (South Korean Center for the Validation of Alternative Strategies) at the National Institute of Environmental Wellness Sciences, with ad hoc participation from governmental institutions from Brazil, Singapore, China and Taiwan. With the aim of comparing specifications in diverse jurisdictions and coordinating the promotion and in the end the implementation of non-animal approaches worldwide, a summary of regulatory needs for skin sensitisation testing across the countries represented by the ICATM partners was published (Daniel et al. 2018), together having a proposal of practical approaches to promote the adoption and regulatory use of defined approaches (DAs)2 for the assessment of skin sensitisation (Casati et al. 2018). Right here we summarise present EU regulatory requirements for the human well being assessment of chemical compounds beneath Attain and also the Cosmetic Products Regulation, contemplating the following toxicological endpoints: skin corrosion and irritation, serious eye damage/eye irritation, photo-induced toxicity, mutagenicity/genotoxicity, acute toxicity, skin sensitisation, repeated dose toxicity, carcinogenicity, reproductive anddevelopmental toxicity, also as absorption, distribution, metabolism and excretion (ADME) and toxicokinetics (TK), and recognize the main challenges in current regulatory testing practice. We widen the discussion around the availability and advancement of new technologies and in vitro (non-animal) models, highlighting how new frameworks and initiatives undertaken at the European and international level could help to promote the 3Rs and implement twent.