The assessment of chemical degradation rates from water-sediment experiments like for instance OECD 308 is challenging due to parallel occurrence of processes like degradation, sorption and diffusive transport, at different rates in water and sediment or at their interface. To systematically and quantitatively analyse this limitation, we generated artificial experiment datasets using model simulations and then used these datasets in an inverse modelling exercise to estimate degradation half-lives in water and sediment (DegT50wat and DegT50sed), which then were evaluated against their true values. Results were visualised by chemical space diagrams that identified those substance property combinations for which the OECD 308 test is fundamentally inappropriate. We show that the uncertainty in estimated degradation half-lives in water increases as the process of diffusion to the sediment becomes dominant over degradation in the water. We show that in theory the uncertainty in the estimated DegT50sed is smaller than the uncertainty in the DegT50wat. The predictive value of our chemical space diagrams was validated using literature transformation rates and their uncertainties that were inferred from real water-sediment experiments.