Calculation of a permitted daily exposure value for the solvent 2-methyltetrahydrofuran

In response to increasing concerns around the potential environmental impact of industrial chemicals, the pharmaceutical industry is seeking alternatives for traditional solvents used during the manufacturing process. Taking into consideration the principles of green chemistry, 2-methyltetrahydrofuran (2-MeTHF) is proposed as a suitable replacement for the structurally similar solvent tetrahydrofuran (THF). 2-MeTHF is derived from renewable sources and is more easily recovered thereby facilitating its reuse. However, 2-MeTHF is currently not included in the International Conference on Harmonisation (ICH) Q3C residual solvent guidelines and there is no Permitted Daily Exposure (PDE) limit proposed below which there would be negligible safety concerns for patients exposed to it as a residual impurity in a drug product.