6-acetyl-1,1,2,4,4,7-hexamethyltetraline (AHTN) induces abnormal macrophage polarization and nuclear lamina...

Synthetic musks (SMs) are detected widely in personal care product samples in China, where 6-acetyl-1,1,2,4,4,7-hexamethyltetraline with tonalide (AHTN) shows the highest detection frequency. This study performed in vivo investigation on immunotoxicity induced by low-dosage and long-term AHTN exposure. The results showed that AHTN exposure disrupted the tightly regulated immune polarization process before pathological damage to other organs. Low-dosage exposure of AHTN initially drove immune cells into the M1 pro-inflammatory phase, followed by mild upregulation of the JAK-STAT pathway to facilitate a shift into the M2 anti-inflammatory phase. In this process, SUN1/2, Nesprin1/2 and Lamin A/C expression were enhanced to preserve nuclear integrity. Higher dosage exposure led to strong inflammation associated with TLR4-MyD88-dependent NF-κB activation, indicated by inctrease in TNF-α and IL-1β, along with lower decrease in IL-4 and IL-10. Lamin A/C was downregulated to promote nuclear lamina disassembly and oxidative stress. This study advances the health risk assessment of environmental contaminants toward earlier detection and intervention of immunotoxicity.