A pilot study of metabolites of organophosphorus flame retardants in paired maternal urine and amniotic fluid samples: potential exposure risks of tributyl phosphate to pregnant women.

Organophosphorus flame retardants (OPs) are of wide concern due to their presence in human urine and their considerable endocrine disruption and neuro-development toxicity. It has been confirmed that electronic waste (e-waste) dismantling activities have contributed to human exposure to OPs. However, assessments of OP exposure and the health risks for pregnant women and fetuses living in areas associated with e-waste dismantling have been impeded by a lack of data. In this study, six OP metabolites (mOPs) were measured in paired maternal urine and amniotic fluid samples collected from an e-waste dismantling area in Guangdong Province, China. All mOPs were detectable in maternal urine, whereas two were found in amniotic fluid. Dibutyl phosphate (DBP) was the predominant mOP in both maternal urine (geometric mean (GM): 2.9 ng ml-1) and amniotic fluid (1.3 ng ml-1); and diphenyl phosphate (DPHP) was the secondary one found (0.94 ng ml-1 in maternal urine, 0.12 ng ml-1 in amniotic fluid). The GM urinary concentrations of DBP and DPHP were two and seven times higher than those in amniotic fluid, respectively. The estimated daily intakes (EDIs) of triphenyl phosphate (TPHP) and tributyl phosphate (TnBP) by pregnant women were calculated from their daily urine excretion rate as fractions of OP metabolized to the corresponding metabolite (FUE). Our results showed high exposure levels to TPHP (median: 273 or 613 ng per kg bw per day) and TnBP (404 ng per kg bw per day) for pregnant women living in the e-waste associated area. Most importantly, 13% of mothers had EDITnBP levels that exceeded the reference dose (RfD: 2400 ng per kg bw per day), suggesting potential health risks from TnBP exposure for pregnant women living in areas associated with e-waste dismantling. This study, as a pilot study, presents the first measurements of mOPs in human amniotic fluid.

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 (TDIHLM) or S9 fraction (TDIS9). 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.