Medium-Chain Chlorinated Paraffins Altered Neurobehavior and Induced Neuroinflammation Associated with Disordered Intestinal Homeostasis

Chlorinated paraffins, derivatives of chlorinated n-alkanes, are widely used in agricultural and industrial applications. With the restriction of short-chain chlorinated paraffins (SCCPs), the use of medium-chain chlorinated paraffins (MCCPs) has sharply increased. MCCPs have recently been detected in foods and animal brains, raising concerns about their health effects. However, their impact on intestinal homeostasis and the nervous system is poorly understood. In this study, neurobehavioral, metabolomics, histopathology, inflammatory responses, gut microbiota, and derived metabolites were evaluated after CP-52 (a commercially prevalent MCCP) exposure. The results showed that CP-52 induced abnormal behaviors, reduced gray matter thickness, activated astrocytes, and triggered neuroinflammation. Concurrently, CP-52 significantly altered gut microbiota, reduced short-chain fatty acid (SCFAs) levels, and promoted intestinal inflammation, potentially contributing to neuroinflammation via the microbiota–gut–brain axis. These findings will provide important insights into the safety assessment of MCCPs.