Graphene-based materials (GBMs) have attracted a lot of attention during the last years due to their extraordinary physicochemical properties. These materials are employed in a wide range of fields, including electronic and biomedical applications1,2,3. From a safety perspective, the major risk for human health associated to these materials is currently related to occupational exposure4, being the inhalation and dermal contact the most relevant routes of exposure to GBMs5. In fact, around 90 % of skin diseases associated with occupational settings are represented by irritant and allergic contact dermatitis6. However, the existing information about cutaneous toxicity of GBMs is scarce. Considering the possible risks in the work environment due to the skin irritation potential of these materials, the present study investigated the cutaneous toxicity of a group of GBMs, including small flakes graphene (SFG), large flakes graphene (LFG) and graphene nanoplatelets (GNplatelets). The inclusion of New Approach Methods (NAMs) for skin sensitization into Organization for Economic Co-operation and Development (OECD) has proved to be a good replacement of animal models. This methodology simulates the human exposure by direct epidermal contact to chemicals. Therefore, to evaluate the skin toxicity, the in vitro EpiDerm Skin Irritation Test (EPI-200-SIT) was employed. Following the OECD Test Nº 439 to determine in vitro skin irritation on reconstructed human epidermis (RhE), it was observed that none of the GBMs caused damage to the tissues. According to EU and Globally Harmonized System of Classification and Labelling Chemicals, GHS, (R38 / Category 2 or no label), an irritant is predicted if the viability of the tissues exposed to the test substance is reduced below 50 % of the viability of the controls. In the case of these GBMs, these materials did not reduce the tissues viability, so they can be considered as non-irritant in the tested conditions. These results provide new insights about the skin irritation potential of GBMs with different properties, demonstrating that the hazard assessment using human in vitro models is a critical aspect to increase the knowledge on their potential impact upon human health. This study is part of the project DIAGONAL (H2020, NMBP-16-2020, Grant Agreement no 953152), which aims to address existing gaps at risk assessment, risk management and risk governance levels providing new knowledge on multicomponent nanomaterials and high aspect ratio nanomaterials.