The penetration of organophosphate
triesters (tri-OPEs) and diesters
(di-OPEs) across the blood–brain barrier and their influencing
factors remain unclear in humans. In this study, 21 tri-OPEs and 8
di-OPEs were measured in 288 paired serum and cerebrospinal fluid
(CSF) samples collected in Jinan, China. Six tri-OPEs were frequently
detected in both serum and CSF, with median concentrations ranging
from 0.062 to 1.62 and 0.042–1.11 ng/mL, respectively. Their
penetration efficiencies across the blood–CSF barrier (BCSFB)
(R
CSF/serum, C
CSF/C
serum) were calculated at 0.667–2.80,
and these efficiencies first increased and then decreased with their
log K
ow values. The reduced penetration
efficiencies of triphenyl phosphate (TPHP) and 2-ethylhexyl diphenyl
phosphate (EHDPP) may be attributed to their strong binding affinities
for human serum albumin and p-glycoprotein due to their high hydrophobicity
and aryl structure, as indicated by molecular docking. This suggests
that active efflux transport may be involved in the penetration of
TPHP and EHDPP in addition to passive diffusion similar to the other
four tri-OPEs. Di-OPEs were found in few serum samples and even fewer
CSF samples, indicating their limited BCSFB permeability. This may
be due to their high polarity, low hydrophobicity, and ionic state
in blood. This study has important implications for understanding
the neurotoxicity of tri-OPEs and di-OPEs and the underlying mechanisms.
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