Tris(2-butoxyethyl) Phosphate Research Articles

Association of filaggrin gene mutations and childhood eczema and wheeze with phthalates and phosphorus flame retardants in house dust: The Hokkaido study on Environment and Children's Health

Background and aimExposure to phthalates and phosphorus flame retardants (PFRs) is considered to be a risk factor for asthma and allergies. However, little is known about the contribution of loss-of-function mutations in the gene encoding filaggrin (FLG) gene, which are considered to be predisposing factors for eczema and asthma, to these associations. We investigated the associations between exposure to phthalates and PFRs in dust and eczema/wheeze among Japanese children, taking into consideration loss-of-function mutations in FLG. MethodsThis study was part of the Hokkaido study on Environment and Children's Health. Seven phthalates and 11 PFRs in household dust were measured by gas chromatography–mass spectrometry. Eczema and wheeze were assessed in children aged 7 years using the International Study of Asthma and Allergies in Childhood questionnaire. Eight FLG mutations previously identified in the Japanese population were extracted from cord blood samples. Children with one or more FLG mutations were considered to be positive for FLG mutations. The study included 296 children who had complete data (birth records, FLG mutations, first trimester and 7 years questionnaires, and phthalate/PFR levels). Odds ratios (ORs) and 95% confidential intervals (CIs) of eczema and wheeze were calculated for log-transformed phthalate/PFR levels by logistic regression. We also performed stratified analyses based on FLG mutations. ResultsThe prevalence rates of eczema and wheeze were 20.6% and 13.9%, respectively. Among children without any FLG mutations, tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP) increased the OR of wheeze, (OR: 1.22, CI: 1.00–1.48). Significant p values for trends were found between tris (2-butoxyethyl) phosphate (TBOEP) and eczema and di-iso-nonyl phthalate (DiNP) and eczema among children without any FLG mutations, respectively. ConclusionsDespite our limited sample size and cross-sectional study design, the effects of indoor environmental factors on childhood eczema and wheeze were clearer in children without loss-of-function mutations in FLG than in children with mutations. Children with FLG mutations might already be cared for differently in terms of medication or parental lifestyle. Further studies in larger populations are warranted so that severity of symptoms and combinations of FLG mutations can be investigated.

Organophosphate esters in house dust: A comparative study between Canada, Turkey and Egypt.

Organophosphate esters (OPEs) are commonly used as flame retardants (FRs) and plasticizers. The usage of OPEs has increased recently due to the ban of several brominated flame retardants, but information on levels in the environment, including the indoor environment is still limited. We investigated the occurrence and distribution of 12 OPEs in urban house dust from Vancouver, Canada; Istanbul, Turkey; and Cairo, Egypt. The median ∑OPE concentration was 41.4 μg/g in the Vancouver samples while median levels in Istanbul and Cairo were significantly lower. The median composition profiles of OPEs in Vancouver and Cairo were dominated by tris (2-butoxyethyl) phosphate (TBOEP), accounting for 56 and 92% of total OPEs respectively while it showed a detection frequency of only 14% in Istanbul. Tris (2-chloropropyl) phosphate (TCPP) was the most abundant chlorinated OPE representing 20 and 36% of the total OPEs in Vancouver and Istanbul respectively, but was below the detection limit in the Cairo dust samples. Consistent with other studies, ΣOPE concentrations were ~1 to 2 orders of magnitude higher than PBDEs and currently used flame retardants in the same dust samples. The mean estimated daily intakes (EDI) of ΣOPE from dust were 115, 38 and 9 ng/kg/bw/day in Vancouver, Cairo and Istanbul respectively for toddlers where adults were ~10 times lower. The total toddler OPE intake ranged from 115 to 2900, 38 to 845 and from 9 to 240 ng/kg bw/day across the three cities. TBOEP had the largest contribution to the EDI in both toddler and adults, where toddler TBOEP exposures via dust represented 4% to 80%, 2% to 44% and 0.1% to 6% of the Reference Doses (RfD) in the mean and high intake scenarios for toddlers in Vancouver, Cairo and Istanbul respectively.

Global microRNA and isomiR expression associated with liver metabolism is induced by organophosphorus flame retardant exposure in male Chinese rare minnow (Gobiocypris rarus)

To reveal the adverse effects of organophosphorus flame retardants (OPFRs) on aquatic organisms at the epigenetic level, male Chinese rare minnows were exposed to 0.24 mg/L tris(2‑butoxyethyl) phosphate (TBOEP), 0.04 mg/L tris(1,3‑dichloro‑2‑propyl) phosphate (TDCIPP), or 0.012 mg/L triphenyl phosphate (TPHP) for 14 days. The effects of sub-acute OPFR exposure on liver miRNA and the 3′ isomiR expression profiles of Chinese rare minnows were investigated. Through small RNA sequencing and bioinformatics analysis, a total of 32, 84, and 19 differentially expressed miRNAs were detected for TBOEP, TDCIPP, and TPHP exposure, respectively (p < 0.05). Target prediction of the differentially expressed miRNAs and pathway enrichment analysis indicated that predicted altered mRNAs for all three OPFRs were associated with metabolic pathways, whereas base excision repair was only predicted to be perturbed by the TPHP treatment. In addition, 3′ isomiR-Us were unexpectedly abundant in all groups (e.g., miR-143), and TDCIPP strongly increased the ratio of 3′ isomiR-U expression. Finally, histological examination and metabolic enzyme activity analyses werein agreement with the predicted metabolic pathways. As such, our study indicates that the investigation of epigenetics changes in miRNA gene transcription is a considerable method for the assessment of aquatic toxicity.

Effects of environmentally relevant concentrations of tris (2-butoxyethyl) phosphate on growth and transcription of genes involved in the GH/IGF and HPT axes in zebrafish (Danio rerio)

Tris (2-butoxyethyl) phosphate (TBOEP), as one of the most widely used organophosphate flame retardants (OPFRs), is applied in nearly all manufactured items and materials. It has been reported that TBOEP could cause developmental impairments and disrupt the endocrine regulation of fish growth during acute toxic experiments. However, concentrations to which fish were exposed in these studies were greater than environmentally relevant concentrations ever reported. This study examined effects on growth associated with exposure of zebrafish to 0, 0.1, 1 and 10 μg/L TBOEP during 20–90 days post fertilization (dpf). The changes in growth indicators and bioaccumulation of TBOEP were examined along with the transcription of related genes in the growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis. The average body contents of TBOEP were higher in females than in males in all the exposure groups. Exposure to environmentally relevant concentrations of TBOEP significantly decreased body length and body mass and down-regulated expression of several genes involved in the GH/IGF and HPT axes. Exposure to TBOEP decreased plasma thyroxine (T4) content accompanied by decreased mRNA level of thyrotropin β-subunit (tshβ) in females at 60 dpf, but no effects were observed at 90 dpf. These results suggested that bioaccumulation of TBOEP and down-regulation of genes involved in the GH/IGF axis might be responsible for the observed growth inhibition in zebrafish exposed to TBOEP.

Associations between allergic symptoms and phosphate flame retardants in dust and their urinary metabolites among school children

BackgroundPhosphate flame retardants (PFRs) are ubiquitously detected in indoor environments. Despite increasing health concerns pertaining to PFR exposure, few epidemiological studies have examined PFR exposure and its effect on children's allergies. ObjectivesTo investigate the association between PFRs in house dust, their metabolites in urine, and symptoms of wheeze and allergies among school-aged children. MethodsA total of 128 elementary school-aged children were enrolled. House dust samples were collected from upper-surface objects. Urine samples were collected from the first morning void. Levels of 11 PFRs in dust and 14 PFR metabolites in urine were measured. Parent-reported symptoms of wheeze, rhinoconjunctivitis, and eczema were evaluated using the International Study of Asthma and Allergies in Childhood questionnaire. The odds ratios (ORs) of the Ln transformed PFR concentrations and categorical values were calculated using a logistic regression model adjusted for sex, grade, dampness index, annual house income, and creatinine level (for PFR metabolites only). ResultsThe prevalence rates of wheeze, rhinoconjunctivitis, and eczema were 22.7%, 36.7%, and 28.1%, respectively. A significant association between tris(1,3-dichloroisopropyl) phosphate (TDCIPP) in dust and eczema was observed: OR (95% confidence interval), 1.44 (1.13–1.82) (>limit of detection (LOD) vs <LOD). The ORs for rhinoconjunctivitis (OR = 5.01 [1.53–16.5]) and for at least one symptom of allergy (OR = 3.87 [1.22–12.3]) in the 4th quartile of Σtris(2-chloro-isopropyl) phosphate (TCIPP) metabolites was significantly higher than those in the 1st quartile, with significant p-values for trend (Ptrend) (0.013 and 0.024, respectively). A high OR of 2.86 (1.04–7.85) (>LOD vs <LOD) was found for hydroxy tris(2-butoxyethyl) phosphate (TBOEP)-OH and eczema. OR of the 3rd tertile of bis (1,3-dichloro-2-propyl) phosphate (BDCIPP) was higher than the 1st tertile as a reference for at least one symptom (OR = 3.91 [1.25–12.3]), with a significant Ptrend = 0.020. ConclusionsWe found that TDCIPP in house dust, and metabolites of TDCIPP, TBOEP and TCIPP were associated with children's allergic symptoms. Despite some limitations of this study, these results indicate that children's exposure to PFR may impact their allergic symptoms.

ORGANOPHOSPHATE ESTERS REMOVAL BY UV/H2 O2 PROCESS MONITORED BY 31P NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

Abstract The present work aims to study the photocatalytic degradation of three organophosphate esters considered environmental emerging contaminants by the UV/H2O2 system with the use of 31P NMR spectroscopy to investigative their removal after the treatment. Results demonstrated the efficiency of the oxidation system in removing the esters tris(2-butoxyethyl) phosphate (TBEP), tris(2-chloroethyl) phosphate (TCEP) and tri-butyl phosphate (TBP) from aqueous solutions when they were individually present and mixed. High levels of degradation of these chemicals were achieved, in addition to the good performance of the analytical technique applied in the study, which represents some advantages in comparison with other techniques reported in the literature. An increase in the 31P NMR signal removal could also be observed when the oxidizing agent concentration increases. Decreases in solution acute toxicity were also verified for both TBP and TBEP treated samples when compared with the samples before the treatment.

Investigation of Daphnia magna Sub-Lethal Exposure to Organophosphate Esters in the Presence of Dissolved Organic Matter Using ¹H NMR-Based Metabolomics.

Organophosphate esters (OPEs) are frequently detected in aquatic environments. Hydrophobic OPEs with high octanol-water partition coefficients (Log KOW) will likely sorb to dissolved organic matter (DOM) and consequently alter OPE bioavailability and sub-lethal toxicity. 1H nuclear magnetic resonance (NMR)-based metabolomics was used to evaluate how DOM (5 mg organic carbon/L) alters the metabolic response of Daphnia magna exposed to sub-lethal concentrations of three individual OPEs with varying hydrophobicity. D. magna exposed to the hydrophilic contaminant (Log KOW = 1.43) tris(2-chloroethyl) phosphate (TCEP) did not have substantial metabolic changes and DOM did not alter the metabolic response. There were significant increases in amino acids and a decrease in glucose from exposure to the hydrophobic contaminant (Log KOW = 3.65) tris(2-butoxyethyl) phosphate (TBOEP) which DOM did not mitigate, likely due to the high sub-lethal toxicity of TBOEP. Exposure to DOM and the hydrophobic contaminant (Log KOW = 4.76) triphenyl phosphate (TPhP) resulted in a unique metabolic response which was unlike TPhP only exposure, perhaps because DOM may be an additional stressor with TPhP exposure. Therefore, Log KOW values may not always predict how sub-lethal contaminant toxicity will change with DOM and there should be more consideration to incorporate DOM in sub-lethal ecotoxicology testing.

The neuropeptides of Asian freshwater clam (Corbicula fluminea) as new molecular biomarker basing on the responses of organophosphate chemicals exposure

In the present study, to discover new biomarker of Asian freshwater clam (Corbicula fluminea) to assess impact of environmental pollutions, cholecystokinin (CCK), conopressin, and Neuropeptide FF (FFamide) in C. fluminea were selected as potent biomarkers. Therefore, their full-length cDNAs were cloned and characterized to investigate the molecular characteristics and expression patterns of neuropeptides in C. fluminea. According to the sequence analysis, CCK, conopressin, and FFamide encoded proteins of 173, 152, and 90 amino acids, respectively. Moreover, the multiple sequence alignment revealed that the bioactive regions of these neuropeptides were well conserved among different invertebrates. In addition, under basal conditions, CCK, conopressin and FFamide mRNA were mainly expressed in the visceral mass, whereas the FFamide mRNA was rarely detected in the foot and mantle. Exposure to 20 and 200 μg/L Tris (2-butoxyethyl) phosphate (TBOEP) and tri-butyl-phosphate (TBP) exposure significantly up-regulated the expression of the CCK and FFamide mRNAs in the visceral mass (p < 0.05), whereas no significant changes in conopressin mRNA levels were observed in response to any treatment. Therefore, CCK and FFamide of C. fluminea neuropeptides are feasible new biomarkers for screening and assessing responses to organophosphate chemicals.

Concentrations and variability of organophosphate esters, halogenated flame retardants, and polybrominated diphenyl ethers in indoor and outdoor air in Stockholm, Sweden

We investigated the concentrations and temporal variability of organophospate esters (OPEs), halogenated flame retardants (HFRs) and polybrominated diphenyl ethers (PBDEs) in indoor and outdoor urban air in Stockholm, Sweden over one year (2014–2015) period. The median concentrations of the three target chemical groups (OPEs, HFRs, PBDEs) were 1–2 orders of magnitude higher in indoor air than outdoor urban air. OPEs were the most abundant target FRs with median concentrations in indoor (Σ10OPE = 340 000 pg/m3) and outdoor urban (Σ10OPEs = 3100 pg/m3) air, being 3 orders of magnitude greater than for HFRs in indoor (Σ15HFRs = 120 pg/m3) and outdoor urban (Σ15HFRs = 1.6 pg/m3) air. In indoor air, PBDE concentrations (Σ17PBDEs = 33 pg/m3) were lower than for the HFRs, but in outdoor urban air, concentrations (Σ17PBDEs = 1.1 pg/m3) were similar to HFRs. The most abundant OPEs in both the indoor and outdoor urban air were tris(2-butoxyethyl)phosphate (TBOEP), tris(chloroisopropyl)phosphate (TCIPP), tris(2-chloroethyl)phosphate (TCEP), tri-n-butyl-phosphate (TnBP), triphenyl phosphate (TPhP) and tris(1,3-dichloroisopropyl)phosphate (TDCIPP). TCIPP in indoor air was found in the highest concentrations and showed the greatest temporal variability, which ranged from 85 000 to 1 900 000 pg/m3 during the one-year sampling period. We speculate that activities in the building, e.g. floor cleaning, polishing, construction, introduction of new electronics and changes in ventilation rate could explain its variation. Some OPEs (TnBP, TCEP, TCIPP, TDCIPP and TPhP), HFRs/PBDEs (pentabromotoluene, 2, 3-dibromopropyl 2, 4, 6-tribromophenyl ether, hexabromobenzene, BDE-28, -47, and -99) in outdoor urban air showed seasonality, with increased concentrations during the warm period (p < 0.05, Pearson's r ranged from −0.45 to −0.91). The observed seasonality for OPEs was probably due to changes in primary emission, and those for the HFRs and PBDEs was likely due to re-volatilization from contaminated surfaces.

Evaluation of the current contamination status of PFASs and OPFRs in South Korean tap water associated with its origin

We investigated the concentrations of perfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs) in 44 tap water samples, collected from eight major cities in South Korea served by four representative watersheds, to evaluate the water contamination status. The total concentrations of PFASs and OPFRs ranged from 1.44 to 224ng/L (median=11.9ng/L), and 74.0 to 342ng/L (median=151ng/L), respectively. The predominant compounds in tap water were perfluorohexane sulfonate (PFHxS), perfluoropentanoic acid (PFPeA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), tris(2-chloroethyl) phosphate (TCEP), tris(chloroisopropyl) phosphate (TCIPP), and tris(2-butoxyethyl) phosphate (TBOEP). Tap water originating from the Nakdong River within an industrial complex showed a notably higher PFHxS proportion to total PFASs. In addition, significantly higher PFAS levels were found in river-originating tap water than in lake/reservoir-originating tap water (Mann-Whitney U test, p<0.05). Meanwhile, major OPFRs showed no clear difference in distribution by region, and no significant difference in major OPFR levels was observed according to tap water origin. Finally, the average human exposure via tap water consumption was estimated for PFASs (46.8ng/person/day) and OPFRs (254ng/person/day).

Occurrence and Distribution of Organophosphate Flame Retardants/Plasticizers in Surface Waters, Tap Water, and Rainwater: Implications for Human Exposure

The occurrence and profiles of 14 triester organophosphate flame retardants (OPFRs) and plasticizers were investigated in surface water, tap water, rainwater, and seawater collected from New York State. In total, 150 samples collected from rivers ( n = 35), lakes ( n = 39), tap water ( n = 58), precipitation/rainwater ( n = 15), and seawater ( n = 3) were analyzed for 14 organophosphate esters (OPEs). An additional nine Hudson River water samples were collected periodically to delineate seasonal trends in OPE levels. The total concentrations of OPEs were found at part-per-trillion ranges, with average concentrations that ranged from 0.01 ng/L for tripropyl phosphate (TPP) in river water to 689 ng/L for tris(2-butoxyethyl)phosphate (TBOEP) in lake water. Tris(1-chloro-2-propyl)phosphate (TCIPP) was the most abundant compound among the investigated OPEs in all types of water. The concentrations of OPEs in river-, lake-, and rainwater were similar but >3 times higher than those found in tap water. Chlorinated alkyl OPFRs accounted for a major proportion of total concentrations. TCIPP, TBOEP, and triethyl phosphate (TEP) were found in >90% of the samples analyzed. Wet deposition fluxes for 14 OPFRs were estimated, on the basis of the concentrations measured in rainwater in Albany, New York, and the values were between 440 and 5250 ng/m2. Among several surface water bodies analyzed, samples from the Hudson River and Onondaga Lake contained elevated concentrations of OPEs. Estimated daily intake of OPEs via the ingestion of drinking water was up to 9.65 ng/kg body weight/day.

Brominated Flame Retardants and Organophosphate Esters in Preschool Dust and Children's Hand Wipes.

Children spend a considerable part of their day in preschool, where they may be exposed to hazardous chemicals in indoor dust. In this study, brominated flame retardants (BFRs) and organophosphate esters (OPEs) were analyzed in preschool dust ( n = 100) and children's hand wipe samples ( n = 100), and diphenyl phosphate (DPHP) was analyzed in urine ( n = 113). Here we assessed children's exposure via dust, identified predictors for chemicals in dust, and studied correlations between different exposure measures. The most abundant BFRs in dust were decabromodiphenyl ether (BDE-209) and decabromodiphenyl ethane (DBDPE) found at median levels of 270 and 110 ng/g dust, respectively. Tris(2-butoxyethyl) phosphate (TBOEP) was the most abundant OPE, found at a median level of 79 000 ng/g dust. For all OPEs and some BFRs, there were significant correlations between the levels in dust and hand wipes. In addition, triphenyl phosphate (TPHP) in preschool dust was significantly correlated with the corresponding metabolite DPHP in children's urine. The levels of pentaBDEs in dust were higher in older preschools compared with newer, whereas levels of DBDPE were higher in newer preschools. Children's estimated intakes of individual BFRs and OPEs via preschool dust were below available health-based reference values. However, there are uncertainties about the potential health effects of some emerging BFRs and OPEs.

Tris (2-butoxyethyl) phosphate affects motor behavior and axonal growth in zebrafish (Danio rerio) larvae

Tris (2-butoxyethyl) phosphate (TBOEP) is an environmental contaminant that poses serious risks to aquatic organisms and their associated ecosystem. Recently, the reproductive and developmental toxicology of TBOEP has been reported. However, fewer studies have assessed the neurotoxic effects in zebrafish (Danio rerio) larvae. In this study, zebrafish embryos were subjected to waterborne exposure of TBOEP at 0, 50, 500, 1500 and 2500 μg/L from 2 to 144-h post-fertilization (hpf). Behavioral measurements showed that TBOEP exposure reduced embryonic spontaneous movement and decreased swimming speed of larvae in response to dark stimulation. In accordance with these motor effects, TBOEP treatment reduced neuron-specific GFP expression in transgenic Tg (HuC-GFP) zebrafish larvae and inhibited the growth of secondary motoneurons, as well as decreased expression of marker genes related to central nervous system development in TBOEP treated group. Furthermore, increased concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as reduction of SOD activity were detected in TBOEP exposure group. The present results showed that the alteration in motor neuron and oxidative stress could together lead to the motor behavior alterations induced by TBOEP.

Characterized in Vitro Metabolism Kinetics of Alkyl Organophosphate Esters in Fish Liver and Intestinal Microsomes.

Tris(2-butoxyethyl) phosphate (TBOEP) and tris( n-butyl) phosphate (TNBP) are the most commonly used alkyl organophosphate esters (alkyl-OPEs), and they increasingly accumulate in organisms and create potential health hazards. This study examined the metabolism of TNBP and TBOEP in Carassius carassius liver and intestinal microsomes and the production of their corresponding monohydroxylated and dealkylated metabolites. After 140 min of incubation with fish liver microsomes, the rapid depletion of TNBP and TBOEP were both best fitted to the Michaelis-Menten model (at administrated concentrations ranging from 0.5 to 200 μM), with a CLint (intrinsic clearance) of 3.1 and 3.9 μL·min-1·mg-1 protein, respectively. But no significant ( P > 0.05) biotransformation was observed for these compounds in intestinal microsomes at any administrated concentrations. In fish liver microsomes assay, bis(2-butoxyethyl) hydroxyethyl phosphate (BBOEHEP) and bis(2-butoxyethyl) 3-hydroxyl-2-butoxyethyl phosphate (3-OH-TBOEP) were the most abundant metabolites of TBOEP, and dibutyl-3-hydroxybutyl phosphate (3-OH-TNBP) was the predominant metabolite of TNBP. Similarly, the apparent Vmax values (maximum metabolic rate) of BBOEHEP and 3-OH-TNBP were also respectively highest among those of other metabolites. Further inhibition studies were conducted to identify the specific cytochrome P450 (CYP450) isozymes involved in the metabolism of TNBP and TBOEP in liver microsomes. It was confirmed that CYP3A4 and CYP1Awere the significant CYP450 isoforms catalyzing the metabolism of TNBP and TBOEP in fish liver microsomes. Overall, this study emphasized the importance of hydroxylated metabolites as biomarkers for alkyl-OPEs exposure, and further research is needed to validate the in vivo formation and toxicological implications of these metabolites.

Occurrence and distribution of organophosphorus flame retardants/plasticizers and synthetic musks in sediments from source water in the Pearl River Delta, China.

The Pearl River (China) and its tributaries receive discharges of treated/untreated domestic sewage and industrial wastewater throughout the entire drainage basin. The river provides source water for many local inhabitants, and there is great concern over its pollution status. Fifteen sediment samples were collected from source water areas in the Pearl River Delta, and analyzed for the occurrence and distribution of 2 classes of emerging pollutants, organophosphorus flame retardants (OPs) and synthetic musks. In most sediments, 5 polycyclic musks and 2 nitro musks were detected, and galaxolide (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta (g)-2-benzopyran [HHCB]) and tonalide (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene [AHTN]) were the predominant components, with concentrations of 0.030 to 547 and 4.31 to 439 ng/g, respectively. Seven widely used OPs were found in most sediments, at varying total concentrations from 1.79 to 143 ng/g, with tris(2-butoxyethyl) phosphate (TBEOP), tris(2-chloro-isopropyl) phosphate (TCIPP), and triphenyl phosphate (TPHP) being the main components. The results indicated that industrial discharge and domestic sewage played important roles for synthetic musk and OP distribution in sediments in the study area. In general, higher levels of OPs and synthetic musks were found in Guangzhou, Foshan, and Dongguan, suggesting a significant impact from industrial discharges and the dense population of these regions. Environ Toxicol Chem 2018;37:975-982. © 2017 SETAC.

Methods for the analysis of organophosphorus flame retardants—Comparison of GC-EI-MS, GC-NCI-MS, LC-ESI-MS/MS, and LC-APCI-MS/MS

ABSTRACTOrganophosphorus flame retardants (PFRs) are extensively used as alternatives to banned polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD). In this study, we analyzed 14 PFRs by means of four mass-spectrometry-based methods: gas chromatography combined with electron-impact mass spectrometry (GC-EI-MS) or negative-chemical-ionization mass spectrometry (GC-NCI-MS) and liquid chromatography combined with tandem mass spectrometry using electrospray ionization (LC-ESI-MS/MS) or atmospheric pressure chemical ionization (LC-APCI-MS/MS). The limits of quantification (LOQs) for LC-ESI-MS/MS and LC-APCI-MS/MS (0.81–970 pg) were 1–2 orders of magnitude lower than the LOQs for GC-EI-MS and GC-NCI-MS (2.3–3900 pg). LC-APCI-MS/MS showed the lowest LOQs (mean = 41 pg; median = 3.4 pg) for all but two of the PFRs targeted in this study. For LC-APCI-MS/MS, the lowest LOQ was observed for tributyl phosphate (TBP) (0.81 pg), and the highest was observed for tris(butoxyethyl) phosphate (TBOEP) (36 pg). The results of this study indicate that LC-APCI-MS/MS is the optimum analytical method for the target PFRs, at least in terms of LOQ.

Organophosphate ester (OPEs) flame retardants and plasticizers in air and soil from a highly industrialized city in Turkey

Passive air samples were collected at eight sites in Bursa, Turkey during five sampling periods between February–December 2014. Locations encompassed urban, suburban, industrial, rural and background environments. Soil samples (n=8) were collected at each site during February 2014. Six OPEs were detected in samples: tris(2-chloroethyl) phosphate (TCEP), tris(chloropropyl) phosphate (TCPP), triphenyl phosphate (TPHP), tris(2-butoxyethyl) phosphate (TBOEP), tris(2-ethylhexyl) phosphate (TEHP), and tris(2-isopropylphenyl) phosphate (T2iPPP). Frequency of detection in air samples was TCPP and TPHP (100%)>TBOEP (88%)>TCEP (85%)>TEHP (78%)>T2iPPP (20%). Total OPEs in air per site by sampling period (excluding non-detects) ranged from 529 to 19,139pg/m3. In soil, total OPEs ranged from 38 to 468ng/g dw. In air, alkylated OPEs dominated followed by halogenated and aryl OPEs. In air, annual mean concentrations were TBOEP>TCPP>TPHP>T2iPPP>TEHP>TCEP. In soils, alkylated OPEs were dominant at six sites and chlorinated OPEs at two sites. A comparison of OPE profiles between air and soil suggests that soils may be partly a source of OPEs to air. Mean concentrations in air were not directly proportional to temperature, and there were differences between alkylated compared to halogenated and aryl OPEs. In air, total and alkylated OPEs levels were fairly uniform, whereas more variability was found for the halogenated and aryl compounds. The relative contribution to total OPEs decreases for alkylated OPEs and increases for halogenated OPEs in samples going from background to suburban to urban and industrial sites. Levels of individual OPEs were all positively correlated between air and soils. In air, correlations between individual compounds were weak to moderate and were only statistically significant for TBOEP and TPHP. In soils, correlations were generally stronger and statistically significant only for TPHP and T2iPPP.

Legacy and emerging organophosphοrus flame retardants in car dust from Greece: Implications for human exposure

Organophosphorus flame retardants (PFRs) and emerging PFRs (ePFRs) are two groups of compounds used as replacements for brominated flame retardants (BFRs). They have already been detected in indoor dust (mainly in homes and offices). To date, few studies investigated the occurrence of FRs in car dust and the information of possible health risks is still limited. The present study reports on the investigation of the levels and profiles of eight target PFRs: tris(2-ethylhexyl) phosphate (TEHP), tris(2-chloroethyl) phosphate (TCEP), tris(2-butoxyethyl) phosphate (TBEP), triphenyl phosphate (TPHP), 2-ethylhexyl diphenyl phosphate (EHDPHP), tris(1-chloro-2-propyl) phosphate (TCIPP), tri cresyl phosphate (TCP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and four target ePFRs; 2,2-bis(chloromethyl)propane-1,3-diyltetrakis(2-chloroethyl)bisphosphate (V6), isodecyl diphenyl phosphate (iDDPHP), resorcinol bis(diphenylphosphate) (RDP) and bisphenol A-bis(diphenyl phosphate) (BDP) in car dust from Greece. The samples were collected from the interior of 25 private cars in Thessaloniki, Greece, with different years of manufacture (1997–2015) and continents of origin. After ultrasonic extraction and Florisil fractionation, the PFR analysis was carried out by GC-EI/MS, whereas the ePFRs were analyzed by LC-MS/MS. Levels of Σ8PFRs varied from 2000 to 190,000 ng g−1, with mean and median concentrations of 20,000 and 11,500 ng g−1, respectively. The concentrations of Σ4ePFRs ranged from 44 to 8700 ng g−1, with mean and median values at 1100 and 190 ng g−1, respectively. Estimations of human exposure showed that toddlers are more exposed than adults to both PFRs and ePFRs. Yet, the intake via dust ingestion and dermal absorption was several orders of magnitude lower than the corresponding reference doses.

Occurrence and human exposure to brominated and organophosphorus flame retardants via indoor dust in a Brazilian city.

Indoor dust is considered an important human exposure route to flame retardants (FRs), which has arised concern due the toxic properties of some of these substances. In this study, ten organophosphorus flame retardants (OPFRs), eight polybrominated diphenyl ethers (PBDEs) and four new brominated flame retardants (NBFRs) were determined in indoor dust from different places in Araraquara-SP (Brazil). The sampled places included houses, apartments, offices, primary schools and cars. The analysis of the sample extracts was performed by gas chromatography coupled to mass spectrometry and two ionization techniques were used (electron ionization - EI; electron capture negative ionization - ECNI). OPFRs were the most abundant compounds and tris(2-butoxyethyl) phosphate (TBOEP), tris(phenyl) phosphate (TPHP), tris(1,3-dichloroisopropyl) phosphate (TDCIPP) and tris(2-chloroisopropyl) phosphate (TCIPP) were present at the highest concentrations. Among the brominated FRs, the most ubiquitous compounds were BDE-209, bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP) and decabromodiphenyl ethane (DBDPE). Statistical analysis revealed that there were differences among dust typologies for TBOEP, TDCIPP, ethylhexyl diphenyl phosphate (EHDPHP), BDE-209, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EH-TBB), BEH-TEBP and DBDPE, which were attributed to different construction materials in each particular environment and to the age of the buildings. The highest levels of brominated FRs were observed in offices, TBOEP was at high concentration in primary schools, and TDCIPP was at high concentration in cars. A preliminary risk assessment revealed that toddlers were exposed to TBOEP levels higher than the reference dose when considering the worst case scenario. The results obtained in this study showed for the first time that although Brazil does not regulate the use of FRs, these substances are present in indoor dust at levels similar to the observed in countries that have strict fire safety standards, and that humans are exposed to complex mixtures of these contaminants via indoor dust.

Toxicogenomics of the flame retardant tris (2-butoxyethyl) phosphate in HepG2 cells using RNA-seq

Tris (2-butoxyethyl) phosphate (TBOEP) is a compound produced at high volume that is used as both a flame retardant and a plasticizer. It is persistent and bioaccumulative, yet little is known of its toxicological modes of action. Such insight may aid risk assessment in a weight-of-evidence approach supplementing current testing strategies. We used an RNA sequencing approach as an unbiased and sensitive tool to explore potential negative health effects of sub-cytotoxic concentrations of TBOEP on the transcriptome of the human liver hepatocellular carcinoma cell line, HepG2, with the lowest concentration used potentially holding relevance to human physiological levels. Over-representation and gene set enrichment analysis corresponded well and revealed that TBOEP treatments resulted in an upregulation of genes involved in protein and energy metabolism, along with DNA replication. Such increases in cell and macromolecule metabolism could explain the increase in mitochondrial activity at lower TBOEP concentrations. In addition, TBOEP affected a wide variety of biological processes, the most notable one being the general stress response, wound healing. Finally, TBOEP showed effects on steroid hormone biosynthesis and activation, regulation, and potentiation of immune responses, in agreement with other studies. As such, this study is the first study investigating genome-wide changes in gene transcription in response to TBOEP in human cells.