Container-content interactions are common in the food and pharmaceutical industries. However, these studies are more complicated in the cosmetic industry, and it is necessary to ensure consumer safety. The objective of this work was to develop a strategy for the toxicological evaluation of leachables for cosmetic packagings. Eleven common plastic packagings were selected to evaluate interactions with 5 simulants (acidic, alkaline and neutral water, 30% and 96% ethanol) chosen to mimic cosmetics behavior. A GC-MS method was developed to screen for 12 non-intentionally added substances of particular concern: 10 phthalates, bisphenol A and distearyl thiodipropionate (European Pharmacopoeia plastic additive 17). Results were analyzed using a toxicological procedure established for this study. Some phthalates and bisphenol A were detected in several samples, but only one contaminant, diisobutyl phthalate (DiBP), was found to be above the set concentration threshold. Using toxicological data, this concentration was found to be safe for users. 96% ethanol appeared to be the strongest simulant in term of extraction, with a maximum concentration of 491 μg/L for DiBP in a 100% styrene-acrylonitrile copolymer packaging. In water simulants, less contaminants were extracted, with concentrations under 20 μg/L.