Safe-and-sustainable-by-design (SSbD) is a concept that takes a systems approach by integrating safety, sustainability, and functionality throughout a product’s the life cycle. This paper proposes a framework based on a prospective life cycle assessment for early safety and sustainability assessment. The framework’s purpose is to identify environmental sustainability and toxicity hotspots early in the innovation process for future SSbD applicability. If this is impossible, key performance indicators are assessed. Environmental sustainability aspects, such as global warming potential (GWP) and cumulative energy demand (CED), and toxicity aspects, such as human toxicity potential and freshwater ecotoxicity potential, were assessed upon applying the framework on a case study. The case study regarded using nano-titanium dioxide (P25-TiO2) or a modified nano-coated version (Cu2O-coated/P25-TiO2) as photocatalysts to produce hydrogen from water using sunlight. Although there was a decrease in environmental impact (GWP and CED), the modified nano-coated version had a relatively higher level of human toxicity and freshwater eco-toxicity. For the presented case study, SSbD alternatives need to be considered that improve the photocatalytic activity but are not toxic to the environment. This case study illustrates the importance of performing an early safety and environmental sustainability assessment to avoid the development of toxic alternatives.