Polymer additives, contaminants and non-intentionally added substances in consumer products: Combined migration, permeation and toxicity analyses in skin | Polymeradditive, Kontaminanten und unbeabsichtigt eingebrachte Stoffe in Verbraucherprodukten: Kombinierte Migrations-, Permeations- und Toxizitätsanalysen in Haut

Most people are not aware of the potential health risks associated with the ingredients of daily used polymeric consumer products. The application range is as diverse as the composition of the materials. Polymeric material is exemplarily used in tool handles, food contact materials and toys. It is thus even more important that the final product is harmless to health and ensures safe usage over the entire product life cycle. Analyzing the composition, intentionally added substances need to be distinguished from non-intentionally added substances. Unlike substances that were added for a defined purpose (e.g. plasticizers, antioxidants or processing aids), non-intentionally added substances are present as a result of material aging or inappropriate manufacturing processes (e.g. contaminants, decomposition or reaction products). In this thesis, the focus was on polymeric consumer products that are designated for skin contact. Besides the oral and inhalative route, the dermal path of exposure may pose a major route for xenobiotics to enter the organism. This is of special concern in case of toxicological relevant xenobiotics like polycyclic aromatic hydrocarbons (PAHs), aminobenzene- or cresol-derivatives. There is an EU-wide restriction on 8 PAHs that are classified as presumed to have carcinogenic potential to humans in toys and consumer products effective since 2015 (REACH EG No. 1907/2006, EU No. 1272/2013). Articles shall not be placed on the market if any of their rubber or plastic components that come into direct as well as prolonged or short-term repetitive contact with the human skin contain more than 0.5 mg/kg or 1 mg/kg respectively. The limits set refer to the PAHs content in the material and do not mirror the actual dermal exposure of consumers. Therefore, it is crucial to study the real dermal PAH load in order to generate data for a reliable assessment of potential health risks. In this thesis, dermal exposure to leachables of rubber and elastomers was investigated consequently using excised human skin in the Franz diffusion cell (FDC)-assay. Basing on this reference data, an alternative testing method was developed for dermal exposure assessment of PAHs. It uses a simulant suitable for the lipophilic PAHs and it realistically mirrors the combined permeation and migration of PAHs. Exposure data basing on this method was provided for the European Commission in order to review the limit values of PAHs in consumer products and toys. The skin permeation was visualized at the example of the procarcinogen N-phenyl-2-naphthylamine. Human skin was exposed ex vivo to a polyolefin entailing this antioxidant and a depth profile generated applying ATR-FTIR-microscopy. It was shown by this very graphic evaluation, that numerous polymer additives with in part toxicological relevance might migrate, overcome the skin barrier and ultimately lead to a potential health risk. A detailed characterization of the polymeric material was conducted using broad analytics. The development of multi-analyte-methods allowed quantification of 21 additives, 5 degradation products and 28 PAHs. The polymers were identified applying pyrolysis coupled online to gas chromatography and mass-spectrometric detection. Furthermore, additives were tested in different aging protocols to identify potential degradation products of toxicological relevance. It was shown, that cresol-derivatives are formed as a consequence of degradation of phenolic antioxidants and phthalates are formed by degradation of a phthalate substitute plasticizer. The results of this work can be useful to improve risk identification and to prioritize leachables of elastomers and rubber for risk assessment.