The chemical safety of representative polysaccharide films made with pea starch, organocatalytic acetylated pea starch and pectin was investigated at different migration conditions (20 °C/10 days, 70 °C/2 h) using two official simulants signifying hydrophilic (simulant A, 10% ethanol) or lipophilic (simulant D1, 50% ethanol) foods. Migrating semi-volatile and non-volatile compounds were identified and semi-quantified by ultra-high performance liquid chromatography-trap ion mobility time-of-flight mass spectrometry (UHPLC-TIMS-TOF-MS/MS), whereas their toxicity was evaluated by in silico models based on qualitative structure activity (QSAR). Physicochemical analysis revealed polymer wash-off into the simulants. Migration testing at 70 °C for 2 h using simulant D1 resulted in detectable concentrations of glycerol (≤72.1 mg/kg), monoacetylated maltose (≤6.5 mg/kg), and dibutyl phthalate (DBP) (≤0.5 mg/kg, compliant with the existing legislative migration limits) in samples containing acetylated starch. Migrating 3-β-galactopyranosyl glucose (≤8.9 mg/kg) and 2,5-diketo-D-gluconic acid (≤4.9 mg/kg) were detected at 20 °C/10 days. In-silico toxicity emphasized no significant toxicity and categorized organocatalytic acetylated pea starch of no safety concern.