The Internet-of-Things (IoT) has enabled Industry 4.0 as a new manufacturing paradigm. The envisioned future of Industry 4.0 and Smart Factories is to be highly configurable and composed mainly of the 'things' that are expected to come with some, often partial, assurance guarantees. However, many factories are categorised as safety-critical, e.g. due to the use of heavy machinery or hazardous substances. As such, some of the guarantees provided by the 'things', e.g. related to performance and availability, are deemed as necessary in order to ensure the safety of the manufacturing processes and the resulting products. In this paper, we explore key safety challenges posed by Industry 4.0 and identify the characteristics that its safety assurance should exhibit. We propose a set of safety assurance responsibilities, e.g. system integrators, cloud service providers and `things' suppliers. Finally, we reflect on the desirable modularity of such a safety assurance approach as a basis for cooperative, on-demand and continuous reasoning for Industry 4.0 architectures and services.