Urinary metabolites of organophosphate flame retardants in China: Health risk from tris(2-chloroethyl) phosphate (TCEP) exposure.

Organophosphate esters (OPs) are substitutes for polybrominated diphenyl ether (PBDE) flame retardants. China is the largest producer of OPs globally, with the production rate increasing at 15% annually. Since some OPs are neurodevelopmental and/or carcinogenic toxicants, human exposure is a concern. In this study, concentrations of eight OP metabolites (mOPs) were measured in human urine samples collected from 13 cities located in Northern, Eastern, Southern, and Southwestern China. All target mOPs were frequently detected with detection rates of 50% to 100%, indicating widespread human exposure to OPs. Bis(2-chloroethyl) phosphate (BCEP; median: 0.68 ng/mL), bis(1-chloro-2-propyl) phosphate (BCIPP; 0.30 ng/mL), diphenyl phosphate (DPHP; 0.30 ng/mL), and dibutyl phosphate (DBP; 0.29 ng/mL) were the dominant mOPs across all participants. Regional differences in concentrations (ΣmOPs varied from 0.86 to 3.7 ng/mL) and composition profiles (contribution of chlorinated mOPs to ΣmOPs varied from 35% to 95%) of mOPs were observed within China. In comparison to the concentrations reported worldwide, urinary DPHP and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) levels in China were lower, whereas BCEP and DBP levels were comparable or higher. The total daily intake (TDI) of tris(2-chloroethyl) phosphate (TCEP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) were estimated from daily urine excretion rate and the fraction of OP metabolized in human liver microsomes (TDI) or S9 fraction (TDI). The intake estimates showed that Chinese residents were exposed to TCEP from 96.9 to 46,700 (or 52.2 to 25,200) ng/kg bw/day. Depending on the reference dose, we found that approximately 5% of the individuals exceeded the limit (i.e., 2200 ng/kg bw/day) for TCEP intake. To our knowledge, this is the first nationwide baseline survey to determine urinary levels of mOPs in Chinese residents.