Polychlorinated n-alkanes (PCAs), the main component of chlorinated paraffin mixtures (CPs), are complex industrial chemicals widely used as plasticizers, flame retardants, and additives in numerous commercial products and building materials. Due to their persistence, bioaccumulative potential, and widespread use, PCAs are ubiquitous in environmental and biological matrices. However, their extreme compositional complexity hinders harmonized analytical methodologies and toxicological information, challenging exposure assessment and risk evaluation.

The overall objective of this thesis was to improve the understanding of human exposure to PCAs. To contribute to this goal, the thesis aimed to develop analytical workflows, investigate PCA contamination in indoor environments, assess human exposure, and identify important exposure sources and pathways.

To address analytical challenges, CPxplorer, a harmonized high-resolution mass spectrometry-based data analysis workflow, was developed for the identification and quantification of PCAs and related compounds. The workflow was successfully applied across different instrumental platforms and matrices, including indoor dust, indoor organic films (IOFs), silicone wristbands (SWBs), food, and human serum, improving analytical consistency and comparability.

Indoor dust and IOFs collected from Swedish homes, schools, offices, and sport halls revealed widespread PCA contamination. Medium-chain PCAs (ΣPCAs-C_14–17) dominated most indoor matrices, while differences between dust and IOFs reflected matrix-specific partitioning and accumulation processes. Ventilation, cleaning practices, and indoor activities influenced PCA concentrations and patterns, although no single factor fully explained the observed variability.

Human exposure assessment demonstrated that PCA exposure is highly multipathway. Estimated dietary intake exceeded exposure estimates derived from indoor matrices, indicating that food likely represents the major contributor to total external exposure. Nevertheless, chemical forensic fingerprinting analyses showed that PCA homologue patterns measured in serum were more similar to indoor dust and IOFs than to food. Likewise, PCA profiles measured in SWBs were well reconstructed using PCA patterns in indoor environmental matrices, highlighting indoor environments, particularly homes, as important exposure scenarios. These findings suggest that the pathways contributing most to total exposure are not necessarily those most strongly reflected in internal exposure profiles, likely due to variation in homologue-specific bioavailability and toxicokinetics.

Overall, this thesis demonstrates that understanding human exposure to PCAs requires integrated analytical, environmental, and biomonitoring approaches. The results provide new insights into PCA occurrence, partitioning behavior, exposure pathways, and internal exposure patterns, while also contributing methodological tools to support future monitoring, exposure assessment, and regulatory efforts aimed at reducing human exposure to these persistent contaminants.