Abstract

Benzotriazole ultraviolet stabilizers (BUVSs) are widespread environmental contaminants, and their potential neurotoxicity raises a critical public health concern. However, the occurrence of BUVSs in human cerebrospinal fluid (CSF) and matched serum, as well as the penetration of BUVSs across the blood-cerebrospinal fluid barrier (BCSFB) and its influential factors remain unclear, hindering their accurate exposure risk assessment. This study investigated 15 BUVSs in matched human CSF and serum samples from China. Eight BUVSs were detected in human serum, and six BUVSs were detected in CSF. UV-P (2-(2H-benzotriazol-2-yl)- p -cresol) was the most abundant BUVS in both human serum and CSF, showing the mean levels of 6.14   ng/mL and 1.32   ng/mL, respectively. UV-P ( R CSF/serum = 0.31 ± 0.13) had the highest BCSFB penetration ability, followed by UV-329 (2-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)-phenol; 0.21 ± 0.09), UV-326 (2-(3-tert-butyl-2-hydroxy-5-methylphenyl)-5-chloro-2H-benzotriazole; 0.18 ± 0.08), and UV-327 (2-(2’-hydroxy-3’,5’-di-tert-butylphenyl)-5-chloro-benzotriazole; 0.16 ± 0.06). The R CSF/serum values of BUVSs were associated with the lipophilicity (log K ow ) and human serum albumin binding affinity of BUVSs. Notably, integrity of the BCSFB was identified as an important factor impacting the penetration efficiency of BUVSs across the BCSFB. CSF levels of UV-326 and UV-328 (2-(2H-benzotriazol-2-yl)-4,6-ditertpentyl-phenol) were negatively ( p < 0.05) correlated with that of the chloride ion in CSF, suggesting potential neurotoxic implications induced by these BUVSs. Overall, this study represents the first report to document the presence of BUVSs in human CSF, providing direct evidence of their ability to penetrate into the human central nervous system.