Pharmaceutical cellulosic polymers will inevitably reach natural water systems if they are not removed after entering wastewater. Biodegradation of organic chemicals in sewage or in the aquatic environment is an important removal mechanism. In this study, we investigated the environmental biodegradation of 14 cellulose derivatives commonly utilized as pharmaceutical excipients using three different test systems that are based on the closed bottle test (OECD 301D) and the manometric respirometry test (OECD 301F). For the different cellulose derivatives tested, we observed varying degrees of biodegradation ranging from 0 to 20.4 % chemical oxygen demand (COD). However, none met the criteria for classification as ‘readily biodegradable’. In addition, 10 out of 14 cellulose derivatives and/or their possible transformation products formed during the experiments, may exhibit possible toxic inhibitory effects on the inoculum. This includes one or several derivatives of hydroxy propyl methyl cellulose, hydroxy propyl cellulose, methyl cellulose, ethyl cellulose, and hydroxy ethyl cellulose. Based on the results obtained, we have developed a graded classification score (‘traffic light system’) for excipient biodegradation. This could help streamline the assessment and classification of cellulose derivatives concerning risk of persistence and potential adverse environmental effects, thereby assisting in the prioritization of more favorable compounds. In the long term, however, excipients should be designed from the very beginning to be biodegradable and mineralizable in the environment (‘benign by design’).