The production and use of brominated flame retardants have been increasingly restricted. Organophosphate esters (OPEs) have been widely used as substitutes for brominated flame retardants. However, little is yet known about human exposure to OPEs. The potential health risks posed by OPEs were assessed by determining the concentrations of 6 OPEs in pooled serum samples from residents of Shandong, China. The mean ∑ OPE concentrations in 2011 and 2015 were 680 ng/g lipid and 709 ng/g lipid, respectively. The most abundant OPE was tri(2-chloroethyl) phosphate, contributing a mean of 82% of the ∑ OPE concentration. A significant correlation was found between the tri(2-chloroethyl) phosphate and tri-n-butylphosphate concentrations, possibly indicating that these OPEs are used in similar applications and have similar human exposure pathways in the study area. The mean tri(2-chloroethyl) phosphate concentration increased from 536 ng/g lipid in 2011 to 605 ng/g lipid in 2015, but the concentrations of tri-n-butylphosphate, triphenyl phosphate, and tris(methylphenyl) esters decreased between 2011 and 2015. This could indicate that chlorinated OPEs bioaccumulate in humans more strongly than nonchlorinated OPEs do. Environ Toxicol Chem 2017;36:414-421. © 2016 SETAC.

Bone cancer pain (BCP) is a common pathologic pain associated with destruction of bone and pathological reconstruction of nervous system. Current treatment strategies in clinical is inadequate and have unacceptable side effects due to the unclear pathology mechanism. In the present study, we showed that transplantation of Walker 256 cells aggravated mechanical allodynia of BCP rats (**p < 0.01 vs. Sham), and the expression of ASIC3 (Acid-sensitive ion channel 3) and TRPV1 was obviously enhanced in L4-6 dorsal root ganglions (DRGs) of BCP rats (**p < 0.01 vs. Sham). ASIC3 and TRPV1 was mainly expressed in CGRP and IB4 positive neurons of L4-6 DRGs. While, TRPV1 but not ASIC3 was markedly upregulated in L4-6 spinal dorsal horn (SDH) of BCP rats (**p < 0.01 vs. Sham). Importantly, intrathecal injection of CPZ (a TRPV1 inhibitor) or Amiloride (an ASICs antagonist) markedly increased the paw withdraw threshold (PWT) of BCP rats response to Von Frey filaments (**p < 0.01 vs. BCP + NS). What’s more, intraperitoneally injection of Metformin or Vinorelbine markedly elevated the PWT of BCP rats, but reduced the expression of TRPV1 and ASIC3 in L4-6 DRGs and decreased the TRPV1 expression in SDH (*p < 0.05, **p < 0.01 vs. BCP + NS). Collectively, these results suggest an effective analgesic effect of Metformin on mechanical allodynia of BCP rats, which may be mediated by the downregulation of ASIC3 and TRPV1.

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