Ubiquity of Synthetic Phenolic Antioxidants in Children’s Cerebrospinal Fluid from South China: First Evidence for Their Penetration across the Blood–Cerebrospinal Fluid Barrier

Abstract

Synthetic phenolic antioxidants (SPAs) and relevant transformation products (TPs) are potentially neurotoxic pollutants to which humans are widely exposed. However, their penetration behavior across the brain barrier and associated exposure to the central nervous system (CNS) remain unknown. This study is the first to investigate a wide range of 30 SPAs and TPs, including emerging SPAs, in matched serum and cerebrospinal fluid (CSF) samples from children in Guangzhou, China. Sixty-two children of either sex aged <14 years with nonbloody CSF and complete clinical information were included. The findings demonstrated the ubiquitous occurrence of many SPAs and TPs, particularly BHT, 2,4-di-tert-butylphenol (DBP), AO 1010, AO 1076, BHT-Q, and BHT-quinol, not only in serum but also in the CSF. Median total concentrations of SPAs and TPs were up to 22.0 and 2.63 ng/mL in serum and 14.5 and 2.11 ng/mL in CSF, respectively. On calculating the penetration efficiencies across the blood−CSF barrier (BCSFB) (R CSF/serum , C CSF /C serum) for selected SPAs and TPs, their R CSF/serum values (median 0.52− 1.41) were highly related to their physicochemical properties, indicating that passive diffusion may be the potential mechanism of BCSFB penetration. In addition, the R CSF/serum values were positively correlated with the barrier permeability index R Alb (Albumin CSF /Albumin serum ), indicating that barrier integrity is an important determinant of BCSFB penetration. Overall, these results will improve our perception of human internal exposure to SPAs and lay a solid foundation for assessing the risk of CNS exposure to various SPAs.