Levels of Blood Organophosphorus Flame Retardants and Association with Changes in Human Sphingolipid Homeostasis

Abstract

While a recent toxicological study has shown that organophosphorus flame retardants (OPFRs) may disrupt sphingolipid homeostasis, epidemiologic evidence is currently lacking. In this study, a total of 257 participants were recruited from Shenzhen, China. Eleven OPFRs were for the first time simultaneously determined in the human blood samples by ultraperformance liquid chromatography and tandem mass spectrometry. Six OPFRs, tributyl phosphate (TNBP), 2-ethylhexyl diphenyl phosphate (EHDPP), tris(2-chloroisopropyl) phosphate (TCIPP), tris(2-butoxyethyl) phosphate (TBOEP), triethyl phosphate (TEP), and TPHP, were detectable in at least 90% of participants, with median concentrations of 37.8, 1.22, 0.71, 0.54, 0.49, and 0.43 ng/mL, respectively. Sphingomyelin (SM) levels in the highest quartile of EHDPP, TPHP, TNBP, TBOEP, TEP, and TCIPP were 45.3% [95% confidence interval; 38.1%, 53.0%], 51.9% (45.5%, 58.6%), 153.6% (145.1%, 162.3%), 20.6% (14.5%, 27.0%), 59.0% (52.1%, 66.2%), and 62.8% (55.2%, 70.6%) higher than those in the lowest quartile, respectively, after adjusting for covariates. Sphingosine 1-phosphate (S1P) levels in the highest quartile of EHDPP, TPHP, and TNBP were 36% (-39%, -33%), 16% (-19%, -14%), and 36% (-38%, -33%) lower than those in the lowest quartile, respectively. A similar pattern emerged when exposures were modeled continuously. We for the first time found the associations between OPFRs and changes in human sphingolipid homeostasis.

Recent biomonitoring reports on phosphate ester flame retardants: a short review

“…The median concentration of total PEFRs was around 10-100 ng/g of lipids in breast milk from Sweden and several Asian countries, indicating that substantial exposure occurs at a young age via breastfeeding (Sunddkvist et al, 2010;Kim et al, 2014). The parent compounds (Liu et al, 2016;Zhao et al, 2016;Li et al, 2017;Ma et al, 2017;Qiao et al 2017) and their metabolites (Bui et al, 2017) were found in human serum and blood in a few studies. The metabolism of parent PEFRs tends to occur rapidly and the measurement of metabolites concentrations in urine is generally preferred to the invasive measurement of the nonmetabolized chemicals in serum for exposure assessment.…”

Electrospun template directed molecularly imprinted nanofibers incorporated with BiOI nanoflake arrays as photoactive electrode for photoelectrochemical detection of triphenyl phosphate

“…Triphenyl phosphate (TPhP), as a representative of organophosphate flame retardants (OPFRs), has been widely used in a variety of man-made industrial products such as electronic equipments, plastics, textiles, furniture, floor polishes, paints, lubricants, building and insulation materials (Isales et al, 2015;Wang et al, 2014;Zhao et al, 2016). Due to their extensive utilization in household items and consumer and baby products, their ubiquitous occurrence in all environmental matrices has always been detected (Wang et al, 2011;Veen et al, 2012;Wei et al, 2015).…”

Organophosphorus Flame Retardants: A Global Review of Indoor Contamination and Human Exposure in Europe and Epidemiological Evidence

“…Since 2000, 19 epidemiological studies have been assessed, mostly in the USA, on the associations between exposure to OPFRs and health effects in humans, and they are presented in Table 1 [40,[58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74]. The health outcomes studied were reproductive, thyroid, neurodevelopmental, respiratory, immunotoxic and dermal.…”

“…Other outcomes: Blood concentrations of six OPFRs (TCIPP, TBOEP, TPHP, TEP, TNBP and EHDPP) independently increased sphingomyelin concentrations (which participate in cardiovascular function) in blood among adults [70]. Otherwise, TBOEP indoor concentrations in air were associated with an increased risk of sick building syndrome in Japan [73].…”