Abstract Background The EU Horizon2020 “safe-by-design for Nano” (SBD4Nano) project aims to develop a tool to assist users in the safe-by-design process and decisions to reduce risk as a result from working with- or using newly developed products containing manufactured nanomaterials (MNs). Therefore, TNO set out to develop an easy-to-use quantitative exposure assessment tool that helps users with different levels of expertise to reduce the exposure from MNs following an integrated Tiered safe-by-design approach. Method Based on previous projects, literature, expert knowledge, a Tiered set of model determinants and corresponding calculations were integrated into a conceptual model. Also, an exposure database based on the EU GRACIOUS template was created containing a large set of exposure measurements collected from diverse literature studies. Machine learning was applied to these exposure measurements to validate and refine the model. Lastly, a safe-by-design module was added to assist users modify their material or process design to reduce exposure. Results An online tool is realized that will be freely available on https://diamonds.tno.nl/#neq. The NEQ offers a Tiered approach by smartly adapting the questions based on the depth of information the user can provide allowing anywhere between a Tier-1 and a Tier-2 approach. After answering questions, the user is presented an exposure estimate including uncertainty of the current design. The user is guided to enter a new design that reduces the exposure and/or its uncertainty.