From exposure to pathogenesis: A critical review of SCCPs-induced toxicity and potential molecular mechanisms.

Short-chained chlorinated paraffins (SCCPs) are a class of polychlorinated n-alkanes containing 10-13 carbon atoms, which are widely used in several industrial sectors due to their excellent thermal and chemical stability. However, their persistent residues, semi-volatility, and ubiquity in environmental media have raised global concerns. SCCPs are recognized as important environmental pollutants and are listed under the Stockholm Convention on Persistent Organic Pollutants due to their persistence, bioaccumulation, ability to be transported over long distances, and biotoxicity. Despite international restrictions, some developing countries continue to produce and use SCCPs. SCCPs have recently been found to be widely present in human blood, hair, and even in serum samples and umbilical cords of pregnant women. Exposure to SCCPs can lead to metabolic disorder and organ damage, including liver and kidney toxicity, and an increased risk of cancer. Epidemiologic studies have shown a positive correlation between serum levels of SCCPs and biomarkers of certain diseases, suggesting that SCCPs are potentially hazardous to health. Given the global public health implications of chronic exposure to SCCPs, a comprehensive health risk assessment is essential for effective control of health hazards. This review discusses the exposure routes, human accumulation, and mechanisms of toxicity of SCCPs, with a focus on neurologic, thyroid, hepatic, renal, and reproductive toxicity. In particular, the effects of SCCPs on metabolic disorders and signaling pathway perturbations are summarized, as well as the risk of exposure to SCCPs in human samples. Finally, we also look forward to the future direction of SCCPs toxicology research. It is recommended to focus on human exposomics to identify exposure biomarkers, integrate computational toxicology with organoid technologies, and provide scientific basis for SCCPs risk early warning and global management of persistent organic pollutants.