TDCIPP Research Articles

New Details on Organophosphate Flame Retardants: Exposure in Men Appears Stable over Time

A new study evaluating human exposure to two organophosphate flame retardants, tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP), suggests that metabolites from a single urine sample may be useful as biomarkers of longer-term exposure [EHP 121(5):580–585; http://dx.doi.org/10.1289/ehp.1205907]. Both TDCPP and TPP are widely used, and a limited number of animal studies suggest that both compounds may be carcinogenic, neurotoxic, or reproductive toxicants. Despite the potential for health effects, very few human studies of either flame retardant have been published to date, and the authors sought to characterize exposure over time to help inform future exposure assessments. TDCPP and TPP have been used for decades, and their use is believed to have increased since polybrominated diphenyl ether (PBDE) flame retardants were banned in Europe and discontinued in the United States. Like PBDEs, TDCPP and TPP are not chemically bonded to the products they are intended to protect. This allows them to escape into indoor environments such as homes, offices, and car interiors. Indoor dust is known to be a significant source of exposure to PBDEs, and the new study suggests it may also be an important source of exposure to TDCPP, but not TPP. This may be because TPP has many other uses in addition to being a flame retardant in foam furniture padding. The study’s 50 participants were from a larger project involving men recruited from a Boston infertility clinic. The men provided house dust samples, and 45 of them had archived urine samples that were analyzed for flame retardant metabolites. Previously, men from the same study who lived in homes with higher house dust content of TCDPP and TPP were shown to have reduced sperm counts and altered levels of hormones related to fertility and thyroid function. In a new study house dust appeared to be an important source of one organophosphate flame retardant but not the other—at least for men. The primary metabolite of TDCPP is bis(1,3-dichloro-2-propyl) phosphate (BDCPP), and the primary metabolite of TPP is diphenyl phosphate (DPP). Nearly all the house dust samples contained both TDCPP and TPP. The linked urine analysis found BDCPP in 91% of the samples and DPP in 96% of them. Although the highest concentrations of TPP in house dust exceeded the maximum level of TDCPP by 2 orders of magnitude, the pattern was reversed with their metabolites: The highest concentration of BDCPP in the urine samples was 3 times the maximum level of DPP. The researchers also took advantage of a variability subset of the parent study in which men had submitted 9 urine samples over the course of 3 months. Analysis of the multiple samples for 7 men in the substudy indicated that urinary levels were generally stable over time. A single urine sample therefore may predict high exposure groups, although this needs to be confirmed in a larger sample. The authors stress that there may be other sources of significant exposure to TDCPP outside the home, including vehicles and workplaces. They say that future studies should also investigate exposures among women and children, who may differ from men in exposure patterns and susceptibility.

In Ovo Effects of Two Organophosphate Flame Retardants—TCPP and TDCPP—on Pipping Success, Development, mRNA Expression, and Thyroid Hormone Levels in Chicken Embryos

Tris(1-chloro-2-propyl) phosphate (TCPP) and tris(1,3-dichloro-2-propyl) phosphate (TDCPP) are organic flame retardants detected in the environment and biota for which avian toxicological data are limited. In this study, domestic chicken eggs were injected with TCPP or TDCPP (maximum dose = 51,600 and 45,000ng/g egg, respectively) to determine dose-dependent effects on pipping success, development, hepatic messenger RNA (mRNA) expression levels of genes associated with xenobiotic metabolism and the thyroid hormone (TH) pathway, and TH levels following 20-22 days of incubation. Neither compound reduced pipping success; however, TCPP significantly delayed pipping at 9240 and 51,600ng/g and reduced tarsus length at 51,600ng/g. TDCPP exposure resulted in significant decreases in head plus bill length, embryo mass, and gallbladder size at 45,000ng/g and reduced plasma free T4 levels at 7640ng/g. Type I deiodinase, liver fatty acid-binding protein, and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by TCPP, whereas TDCPP induced CYP3A37 and CYP2H1. Chemical analysis of egg contents at incubation days 0, 5, 11, 18, and 19 revealed that > 92% of the injected TCPP or TDCPP concentration was detectable up to day 5; however, < 1% was detected by day 19. The observed phenotypic responses to TCPP and TDCPP exposure may be associated with disruption of the TH axis, which is critical for normal growth and development in birds. The effects of TDCPP on the gallbladder indicate that the disturbance of lipid metabolism is a likely mechanism of toxicity.

Effects of TDCPP or TPP on gene transcriptions and hormones of HPG axis, and their consequences on reproduction in adult zebrafish (Danio rerio)

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP) belong to the group of triester organophosphate flame retardants (OPFRs), which have been used in a wide range of consumer products. These chemicals have been frequently detected in effluents, surface water, and fish, and hence their potential adverse effects on aquatic ecosystem are of concern. The present study was conducted to investigate the reproduction-related effects and possible molecular mechanisms of TDCPP and TPP using a 21 day reproduction test employing adult zebrafish (Danio rerio). After 21 d of exposure to TDCPP or TPP, significant decrease in fecundity along with significant increases of plasma 17β-estradiol (E2) concentrations, vitellogenin (VTG) levels, and E2/testosterone (T) and E2/11-ketotestosterone (11-KT) ratios were observed. The transcriptional profiles of several genes of the hypothalamus–pituitary–gonad (HPG) axis changed as well after the exposure, but the trend was sex-dependent. In male fish, gonadotropin-releasing hormone2 (GnRH2), GnRHR3, cytochrome P450 (CYP) 19B, estrogen receptor α (ERα), ER2 β1, and follicle stimulating hormone β (FSHβ) were upregulated in the brain, while luteinizing hormone β (LHβ) and androgen receptor (AR) were downregulated. Corresponding to the upregulation of FSHβ and downregulation of LHβ in the brain, FSHR was upregulated and LHR was downregulated in the testis. Among the genes that regulate the steroidogenesis pathway, transcription of hydroxyl methyl glutaryl CoA reductase (HMGRA), steroidogenic acute regulatory protein (StAR), and 17β-hydroxysteroid dehydrogenase (17βHSD) decreased, while transcription of CYP11A, CYP17, and CYP19A increased. In female fish, transcription ofGnRH2 and GnRHR3 decreased, but FSHβ, LHβ, CYP19B, ERα, ER2β1, and AR transcription increased in the brain. In the ovary, FSHR and LHR were significantly upregulated, and most steroidogenic genes were significantly upregulated. The observed disruption of GnRH and GtHs could be further related to subsequent disruption in both sex steroid hormone balance and plasma VTG levels, as well as reproductive performance. Overall, our observation indicates that both TDCPP and TPP could disturb the sex hormone balance by altering regulatory mechanisms of the HPG axis, eventually leading to disruption of reproductive performance in fish.

Predictors of tris(1,3-dichloro-2-propyl) phosphate metabolite in the urine of office workers

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is a flame retardant widely used in furniture containing polyurethane foam. It is a carcinogen, endocrine disruptor, and potentially neurotoxic. Our objectives were to characterize exposure of adult office workers (n=29) to TDCPP by measuring its primary metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP), in their urine; measuring TDCPP in dust from their homes; offices and vehicles; and assessing possible predictors of exposure. We identified TDCPP in 99% of dust (GM=4.43μg/g) and BDCPP in 100% of urine samples (GM=408pg/mL). Concentrations of TDCPP were significantly higher in dust from vehicles (GM=12.5μg/g) and offices (GM=6.06μg/g) than in dust from the main living area (GM=4.21μg/g) or bedrooms (GM=1.40μg/g) of worker homes. Urinary BDCPP concentrations among participants who worked in a new office building were 26% of those who worked in older buildings (p=0.01). We found some evidence of a positive trend between urinary BDCPP and TDCPP in office dust that was not observed in the other microenvironments and may be related to the timing of urine sample collection during the afternoon of a workday. Overall our findings suggest that exposure to TDCPP in the work environment is one of the contributors to the personal exposure for office workers. Further research is needed to confirm specific exposure sources (e.g., polyurethane foam), determine the importance of exposure in other microenvironments such as homes and vehicles, and address the inhalation and dermal exposure pathways.

Urinary Metabolites of Organophosphate Flame Retardants: Temporal Variability and Correlations with House Dust Concentrations

Background: A reduction in the use of polybrominated diphenyl ethers (PBDEs) because of human health concerns may result in an increased use of and human exposure to organophosphate flame retardants (OPFRs). Human exposure and health studies of OPFRs are lacking.Objectives: We sought to define the degree of temporal variability in urinary OPFR metabolites in order to inform epidemiologic study design, and to explore a potential primary source of exposure by examining the relationship between OPFRs in house dust and their metabolites in urine.Methods: Nine repeated urine samples were collected from 7 men over the course of 3 months and analyzed for bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and diphenyl phosphate (DPP), metabolites of the OPFRs tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP), respectively. Intraclass correlation coefficients (ICCs) were calculated to characterize temporal reliability. Paired house dust and urine samples were collected from 45 men.Results: BDCPP was detected in 91% of urine samples, and DPP in 96%. Urinary BDCPP showed moderate-to-strong temporal reliability (ICC range, 0.55–0.72). ICCs for DPP were lower, but moderately reliable (range, 0.35–0.51). There was a weak [Spearman r (rS) = 0.31] but significant (p = 0.03) correlation between urinary BDCPP and TDCPP concentrations in house dust that strengthened when nondetects (rS = 0.47) were excluded. There was no correlation between uncorrected DPP and TPP measured in house dust (rS < 0.1).Conclusions: Household dust may be an important source of exposure to TDCPP but not TPP. Urinary concentrations of BDCPP and DPP were moderately to highly reliable within individuals over 3 months.

ICL-IP increases production of polymeric flame retardant for PUR, as TDCP phased out

In the USA, ICL Industrial Products (ICL-IP) is expanding production of polymeric flame retardant Fyrol® HF-5 at its Gallipolis Ferry plant in West Virginia to meet growing market demand in flexible polyurethane (PUR) foam applications. Concurrently, the company is phasing out the production and sale of tris(1,3-dichloro-2-propyl)phosphate (TDCP), known as ‘tris’.

Effects of tris(1,3-dichloro-2-propyl) phosphate and triphenyl phosphate on receptor-associated mRNA expression in zebrafish embryos/larvae

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP) are frequently detected in biota, including fish. However, knowledge of the toxicological and molecular effects of these currently used flame retardants is limited. In the present study, an in vivo screening approach was developed to evaluate effects of TDCPP and TPP on developmental endpoints and receptor-associated expression of mRNA in zebrafish embryos/larvae. Exposure to TDCPP or TPP resulted in significantly smaller rates of hatching and survival, in dose- and time-dependent manners. The median lethal concentration (LC50) was 7.0mg/L for TDCPP and 29.6mg/L for TPP at 120 hour post-fertilization (hpf). Real-time PCR revealed alterations in expression of mRNAs involved in aryl hydrocarbon receptors (AhRs)-, peroxisome proliferator-activated receptor alpha (PPARα)-, estrogenic receptors (ERs)-, thyroid hormone receptor alpha (TRα)-, glucocorticoid receptor (GR)-, and mineralocorticoid receptor (MR)-centered gene networks. Exposure to positive control chemicals significantly altered abundances of mRNA in corresponding receptor-centered gene networks, a result that suggests that it is feasible to use zebrafish embryos/larvae to evaluate effects of chemicals on mRNA expression in these gene networks. Exposure to TDCPP altered transcriptional profiles in all six receptor-centered gene networks, thus exerting multiple toxic effects. TPP was easily metabolized and its potency to change expression of mRNA involved in receptor-centered gene networks was weaker than that of TDCPP. The PPARα- and TRα-centered gene networks might be the primary pathways affected by TPP. Taken together, these results demonstrated that TDCPP and TPP could alter mRNA expression of genes involved in the six receptor-centered gene networks in zebrafish embryos/larvae, and TDCPP seemed to have higher potency in changing the mRNA expression of these genes.

Exposure of zebrafish embryos/larvae to TDCPP alters concentrations of thyroid hormones and transcriptions of genes involved in the hypothalamic–pituitary–thyroid axis

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) has been frequently detected in the environment and in various biota, including fish, and has been implicated in disruption of the thyroid endocrine system. In the present study, zebrafish (Danio rerio) embryos were exposed to different concentrations of TDCPP (10, 50, 100, 300 and 600μg/L) from 2h post-fertilization (hpf) to 144hpf. Developmental endpoints, and whole-body concentrations of thyroid hormones and transcriptional profiles of genes involved in the hypothalamic–pituitary–thyroid (HPT) axis were examined. Exposure to TDCPP caused a dose-dependent developmental toxicity, including decreased body weight, reduced hatching, survival and heartbeat rates, and increased malformation (spinal curvature). Treatment with the positive control chemical 3,3′,5-triiodo-l-thyronine (T3) significantly decreased whole-body thyroxin (T4) concentrations, increased whole-body T3 concentrations, and upregulated mRNA expression involved in the HPT axis as a compensatory mechanism. These results suggested that the HPT axis in 144-hpf zebrafish larvae was responsive to chemical exposure and could be used to evaluate the effects of chemicals on the thyroid endocrine system. TDCPP exposure significantly decreased whole-body T4 concentrations and increased whole-body T3 concentrations, indicating thyroid endocrine disruption. The upregulation of genes related to thyroid hormone metabolism (dio1 and ugt1ab) might be responsible for decreased T4 concentrations. Treatment with TDCPP also significantly increased transcription of genes involved in thyroid hormone synthesis (tshβ, slc5a5 and tg) and thyroid development (hhex, nkx2.1 and pax8) as a compensatory mechanism for decreased T4 concentrations. Taken together, these results suggest that TDCPP alters the transcription of genes involved in the HPT axis and changes whole-body concentrations of thyroid hormones in zebrafish embryos/larvae, thus causing an endocrine disruption of the thyroid system.

Early Zebrafish Embryogenesis Is Susceptible to Developmental TDCPP Exposure

Background: Chlorinated phosphate esters (CPEs) are widely used as additive flame retardants for low-density polyurethane foams and have frequently been detected at elevated concentrations within indoor environmental media.Objectives: To begin characterizing the potential toxicity of CPEs on early vertebrate development, we examined the developmental toxicity of four CPEs used in polyurethane foam: tris(1,3-dichloro-2-propyl) phosphate (TDCPP), tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCPP), and 2,2-bis(chloromethyl)propane-1,3-diyl tetrakis(2-chlorethyl) bis(phosphate) (V6).Methods: Using zebrafish as a model for vertebrate embryogenesis, we first screened the potential teratogenic effects of TDCPP, TCEP, TCPP, and V6 using a developmental toxicity assay. Based on these results, we focused on identification of susceptible windows of developmental TDCPP exposure as well as evaluation of uptake and elimination of TDCPP and bis(1,3-dichloro-2-propyl)phosphate (BDCPP, the primary metabolite) within whole embryos. Finally, because TDCPP-specific genotoxicity assays have, for the most part, been negative in vivo and because zygotic genome remethylation is a key biological event during cleavage, we investigated whether TDCPP altered the status of zygotic genome methylation during early zebrafish embryogenesis.Results: Overall, our findings suggest that the cleavage period during zebrafish embryogenesis is susceptible to TDCPP-induced delays in remethylation of the zygotic genome, a mechanism that may be associated with enhanced developmental toxicity following initiation of TDCPP exposure at the start of cleavage.Conclusions: Our results suggest that further research is needed to better understand the effects of a widely used and detected CPE within susceptible windows of early vertebrate development.

Levels and distributions of organophosphate flame retardants and plasticizers in sediment from Taihu Lake, China

The concentrations and distribution of seven organophosphate flame retardants and plasticizers (OPs) were investigated in 28 sediment samples collected from Taihu Lake. The analytes were ultrasonically extracted, enriched using solid-phase extraction, and determined by gas chromatography-mass spectrometry. The results indicated that the analytes were all detected in the sediments. The total concentrations of seven OPs ranged from 3.38 to 14.25 µg/kg, and tris (2-chloroiso-propyl) phosphate (TCPP), tris (2-chloroethyl) phosphate (TCEP), and tris (2-butoxyethyl) phosphate (TBEP) were the dominant compounds, with concentrations ranging from<limit of quantification to 2.27 µg/kg, 0.62 to 3.17 µg/kg, and 1.03 to 5.00 µg/kg, respectively. The highest concentration of total assessed OPs (14.25 µg/kg) was found at GH-5, with tris (1,3-dichloro-2-propyl) phosphate (TDCPP) as the main component at the sampling site. This result implied that there is an obvious emission source nearby at Suzhou City; in addition, human activities also play an important role in the concentration of OPs in the sediment.

Atmospheric deposition of chlorinated organophosphate flame retardants (OFR) onto soils

This study highlights the influence of dry and wet deposition on concentrations of chlorinated organophosphate flame retardants (OFR) in soil. Soil samples were collected in 2010/11 during a period of snow falling to snow melting, a period of rainfall and a dry period. Snow and rainwater samples were also collected from the soil sampling site. Tris(2-chloroethyl)phosphate (TCEP), tris(2-chloroisopropyl)phosphate (TCPP) and tris(1,3-dichloro-2-propyl)phosphate (TDCP) were analysed in soil samples using a combination of Twisselmann extraction and solid-phase microextraction (SPME), followed by gas chromatography-mass spectrometry (GC-MS). SPME/GC-MS was applied to analyse TCEP, TCPP and TDCP in aqueous samples.Concentrations of TCEP were between 236 and 353ngL−1 in snow and 78 and 234ngL−1 in rain. TCPP concentrations were between 226 and 284ngL−1 in snow and 371 and 385ngL−1 in rain. In soil samples, concentrations ranged from 5.07 to 23.48ngg−1 dry weight (dwt) for TCEP and 5.66 to 19.82ngg−1 dwt for TCPP. Concentrations of TDCP in rainwater and snow samples were rather low (46 and 100ngL−1, respectively); concentrations of TDCP were below the limit of detection in soil samples.Snow melting caused enhanced soil concentrations of TCEP and TCPP, but greater effect of snow melting was observed for TCEP than for TCPP soil concentrations. No significant correlation between precipitation amounts and soil concentrations was observed. The influence of wet deposition on soil contents of TCEP and TCPP may be covered by volatilisation or by the mobility of both compounds in soil and their transport to deeper soil zones with seepage water. Snow was found to be a more efficient scavenger and transporter of chlorinated OFR into soil than rainwater. During dry weather, the soil concentrations of both compounds seemed to be driven mainly by air concentrations, which are determined by source emission strengths and photochemical degradation in the atmosphere.Values of calculated air concentrations were between 0.0034ngm−3 for TCEP and 0.99ngm−3 for TCPP. Total OFR specific loads were 3756ng m-2 day-1 within the first 24h and 3028ng m-2 day-1 within the next 24h. Fugacity calculations (0.011 to 0.103 for TCPP and 0.005 to 0.073 for TCEP) indicated net deposition from air to soil for both compounds.

Endocrine disruption potentials of organophosphate flame retardants and related mechanisms in H295R and MVLN cell lines and in zebrafish

Organophosphate flame retardants (OPFRs) are frequently detected in environment and biota. However, knowledge on their potential toxicological effects is limited. Endocrine disrupting potentials of six OPFRs, i.e., tris-(2-chloroethyl) phosphate (TCEP), tris-(2-chloroisopropyl) phosphate (TCPP), tris-(1,3-dichloro-2-propyl) phosphate (TDCPP), tris-(2-butoxyethyl) phosphate (TBEP), triphenyl phosphate (TPP), and tricresyl phosphate (TCP), were investigated using human cell lines as well as zebrafish (Danio rerio). Sex hormone synthesis and steroidogenic gene transcriptions were measured using H295R cells. With MVLN cells, estrogen receptor binding activities of OPFRs were evaluated. In zebrafish, sex hormones and related gene transcriptions were determined for each sex after 14d exposure to OPFRs. All six OPFRs increased both 17β-estradiol (E2) and testosterone (T) concentrations in H295R cells. In addition, transcription of four major steroidogenic genes was up-regulated and that of two sulfotransferase genes was down-regulated. In MVLN cells, no OPFRs acted as estrogen receptor agonists, while TDCPP, TPP, and TCP acted as antagonists inhibiting binding of E2 to estrogen receptor. After 14d of zebrafish exposure, TCP, TDCPP, or TPP significantly increased plasma T and E2 concentrations, but did not change 11-ketotestosterone (11-KT) among female fish. Among males, both T and 11-KT decreased and E2 increased. In general, transcription of CYP17 and CYP19a genes was significantly up-regulated in both sexes, while vitellogenin (VTG) 1 gene was down- and up-regulated in female and male fish, respectively. The results of this study showed that OPFRs could alter sex hormone balance through several mechanisms including alterations of steroidogenesis or estrogen metabolism.

Effects of Tris(1,3-dichloro-2-propyl) phosphate and Tris(1-chloropropyl) phosphate on Cytotoxicity and mRNA Expression in Primary Cultures of Avian Hepatocytes and Neuronal Cells

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and tris(1-chloropropyl) phosphate (TCPP) belong to a group of chemicals collectively known as triester organophosphate flame retardants (OPFRs). OPFRs are used in a wide range of consumer products and have been detected in biota, including free-living avian species; however, data on toxicological and molecular effects of exposure are limited. An in vitro screening approach was used to compare concentration-dependent effects of TDCPP and TCPP on cytotoxicity and messenger RNA (mRNA) expression in cultured hepatocytes and neuronal cells derived from embryonic chickens. TDCPP was toxic to hepatocytes (LC₅₀ = 60.3 ± 45.8μM) and neuronal cells (LC₅₀ = 28.7 ± 19.1μM), whereas TCPP did not affect viability in either cell type up to the highest concentration administered, 300μM. Real-time reverse transcription-PCR revealed alterations in mRNA abundance of genes associated with phase I and II metabolism, the thyroid hormone (TH) pathway, lipid regulation, and growth in hepatocytes. None of the transcripts measured in neuronal cells (D2, D3, RC3, and Oct-1) varied in response to TDCPP or TCPP exposure. Exposure to ≥ 10μM TDCPP and TCPP resulted in significant upregulation of CYP2H1 (4- to 8-fold), CYP3A37 (13- to 127-fold), and UGT1A9 (3.5- to 7-fold) mRNA levels. Transthyretin was significantly downregulated more than twofold by TCPP at 100μM; however, TDCPP did not alter its expression. Liver fatty acid-binding protein, TH-responsive spot 14-α, and insulin-like growth factor-1 were all downregulated (up to 10-fold) in hepatocytes exposed to ≥ 0.01μM TDCPP and TCPP. Taken together, our results indicate that genes associated with xenobiotic metabolism, the TH pathway, lipid regulation, and growth are vulnerable to TDCPP and TCPP administration in cultured avian hepatocytes. The mRNA expression data were similar to those from a previous study with hexabromocyclododecane.

Concentrations of organophosphate esters and brominated flame retardants in German indoor dust samples

While it is known that the ingestion of indoor dust contributes substantially to human exposure to the recently restricted polybrominated diphenyl ethers (PBDEs), the situation for one class of potential replacements, i.e. organophosphate esters (OPEs), used in a variety of applications including as flame retardants has yet to be fully characterised. In this study, surface dust from twelve different cars from various locations throughout Germany were analysed for eight OPEs, decabromodiphenyl ethane (DBDPE), and eight PBDEs. In five cars, tris-(1,3-dichloro-2-propyl) phosphate (TDCPP) was the dominant compound with concentrations up to 620 μg g(-1) dust. High concentrations of tri-cresyl phosphate (TCP) (up to 150 μg g(-1)) were also detected in two samples of car dust. Dust from ten offices in the same building in Ludwigsburg, Germany was also analysed. In these samples, tri (2-butoxyethyl) phosphate (TBEP) predominated with an average concentration of 7.0 μg g(-1) dust, followed by tris (1-chloro-2-propyl) phosphate (TCPP) at 3.0 μg g(-1) and triphenyl phosphate (TPhP) at 2.5 μg g(-1) dust. Although caution must be exercised given the relatively small database reported here; this study provides evidence that cars and offices from Germany are significantly more contaminated with OPEs than PBDEs. Average concentrations of ΣOPEs were ten times higher in car than in office dust. This is the first study to provide data on a wide range of OPE concentrations in German indoor dust samples.

Complete detoxification of tris(1,3-dichloro-2-propyl) phosphate by mixed two bacteria, Sphingobium sp. strain TCM1 and Arthrobacter sp. strain PY1

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP), a flame retardant, is regarded as a potentially toxic and persistent environmental contaminant. We previously isolated a TDCPP-degrading bacterium, Sphingobium sp. strain TCM1, which, however, produced a toxic metabolite: 1,3-dichloro-2-propanol (1,3-DCP). This study was undertaken to develop a technique for complete TDCPP detoxification using strain TCM1 with a 1,3-DCP-degrading bacterium, Arthrobacter sp. strain PY1. For efficient detoxification, we designed a resting cell system and examined the effect of freezing and lyophilization treatments for preparation of their resting cells. Results show that treatments had no marked adverse effect on their activities. The TDCPP dephosphorylation by TCM1 resting cells was optimal at 30°C and pH 8.5. Also, 1,3-DCP dehalogenation by strain PY1 resting cells was optimal at 35°C and pH 9.5. Under those respective conditions, the activities were 2.48 μmol h⁻¹·OD₆₆₀⁻¹ for TDCPP and 0.95 μmol h⁻¹·OD₆₆₀⁻¹ for 1,3-DCP. Based on these results, we set the reaction temperature to 30°C and pH to 9.0. Then we examined the detoxification of 50 μM TDCPP using mixed resting cells at a final OD(660) of 0.05 for strain TCM1 and 0.2 for strain PY1. In these conditions, TDCPP was eliminated after 1h, but some of the resulting 1,3-DCP remained at a constant level. The increase in strain PY1 cells to a final OD₆₆₀ of 4.0 decreased the TDCPP dephosphorylation rate of strain TCM1 cells but achieved complete detoxification of TDCPP during 12 h of reaction.

Is the PentaBDE replacement, tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a developmental neurotoxicant? Studies in PC12 cells

Organophosphate flame retardants (OPFRs) are used as replacements for the commercial PentaBDE mixture that was phased out in 2004. OPFRs are ubiquitous in the environment and detected at high concentrations in residential dust, suggesting widespread human exposure. OPFRs are structurally similar to neurotoxic organophosphate pesticides, raising concerns about exposure and toxicity to humans. This study evaluated the neurotoxicity of tris (1,3-dichloro-2-propyl) phosphate (TDCPP) compared to the organophosphate pesticide, chlorpyrifos (CPF), a known developmental neurotoxicant. We also tested the neurotoxicity of three structurally similar OPFRs, tris (2-chloroethyl) phosphate (TCEP), tris (1-chloropropyl) phosphate (TCPP), and tris (2,3-dibromopropyl) phosphate (TDBPP), and 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), a major component of PentaBDE. Using undifferentiated and differentiating PC12 cells, changes in DNA synthesis, oxidative stress, differentiation into dopaminergic or cholinergic neurophenotypes, cell number, cell growth and neurite growth were assessed. TDCPP displayed concentration-dependent neurotoxicity, often with effects equivalent to or greater than equimolar concentrations of CPF. TDCPP inhibited DNA synthesis, and all OPFRs decreased cell number and altered neurodifferentiation. Although TDCPP elevated oxidative stress, there was no adverse effect on cell viability or growth. TDCPP and TDBPP promoted differentiation into both neuronal phenotypes, while TCEP and TCPP promoted only the cholinergic phenotype. BDE-47 had no effect on cell number, cell growth or neurite growth. Our results demonstrate that different OPFRs show divergent effects on neurodifferentiation, suggesting the participation of multiple mechanisms of toxicity. Additionally, these data suggest that OPFRs may affect neurodevelopment with similar or greater potency compared to known and suspected neurotoxicants.

Endocrine Damper? Flame Retardants Linked to Male Hormone, Sperm Count Changes

Additive flame retardants such as tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP), which are not chemically bonded to the products they are intended to protect, may escape into indoor environments such as homes, offices, and car interiors. A new study shows that men living in homes with higher amounts of TCDPP and TPP in their house dust had reduced sperm counts and altered levels of hormones related to fertility and thyroid function [EHP 118:318–323; Meeker and Stapleton]. Because the research to date suggests both compounds are ubiquitous in U.S. homes, the study points to a pressing need for further investigation into the sources and levels of day-to-day exposure to the compounds as well as their potential health effects. TDCPP has long been the main flame retardant used in automotive foam cushioning, while TPP has been used for decades in a wide variety of applications, including furniture foam. Since polybrominated diphenyl ether (PBDE) flame retardants were banned in Europe and discontinued in the United States in 2004, the use of alternative flame retardants such as TDCPP and TPP has been on the rise. Indoor dust is known to be an important source of exposure to PBDEs (which also are additive compounds), and the authors suspect this could also be true for other flame retardants. In the current study, TDCPP was found in 96% and TPP in 98% of the house dust samples. As has been reported for other flame retardants found in house dust, the concentrations of the flame retardants in the samples varied markedly, with ranges of < 107–56,090 ng/g for TDCPP and < 173–1,798,100 ng/g for TPP. The concentrations of TDCPP in the men’s homes were comparable to those of PBDEs, whereas the levels of TPP were considerably higher. Because the study participants were part of a larger project involving men recruited from a Boston infertility clinic, the authors had access to information about the men’s reproductive and thyroid hormone levels as well as their semen quality. They estimated associations for an interquartile range (IQR) increase in the level of each chemical measured in the dust samples, adjusting for potential confounders such as age and body mass. IQR analyses reflect the difference between the concentrations at the highest and lowest ends of the middle 50% of exposures. This analysis revealed that each IQR TPP increase in the homes was associated with a 19% decrease in sperm concentrations and a 10% increase in prolactin levels. Increased prolactin can be a marker of decreased dopamine activity and also may be associated with erectile dysfunction. The authors also found that each IQR increase in TDCPP in the homes was associated with a 17% increase in prolactin and a 3% decline in free levels of the thyroid hormone thyroxine. The findings mirror the limited toxicology data available on the study’s end points. They are also consistent with findings on other organophosphate compounds such as the urinary metabolite of the insecticide chlorpyrifos [EHP 112:1665–1670; Meeker et al.]. The authors hope to follow up by exploring human exposure pathways for these flame retardant chemicals and by reassessing these relationships with markers of endocrine function among a greater number of men from the larger ongoing study.

Seasonal fluctuations of organophosphate concentrations in precipitation and storm water runoff

To investigate seasonal fluctuations and trends of organophosphate (flame retardants, plasticizers) concentrations in rain and snow, precipitation samples were collected in 2007–2009 period at a densely populated urban sampling site and two sparsely populated rural sampling sites in middle Germany. In addition, storm water runoff was sampled from May 2008 to April 2009 at an urban storm water holding tank (SWHT). Samples were analyzed for tris(2-chloroethyl) phosphate (TCEP), tris(2-chloro-1-methylethyl) phosphate (TCPP), tris(1,3-dichloro-2-propyl) phosphate (TDCP), tris(2-butoxyethyl) phosphate (TBEP), tri-iso-butyl phosphate (TiBP), and tri-n-butyl phosphate (TnBP) by gas chromatography–mass spectrometry after solid phase extraction. Among the six analyzed organophosphates (OPs), TCPP dominated in all precipitation and SWHT water samples with maximum concentrations exceeding 1000 ng L −1. For all analytes, no seasonal trends were observed at the urban precipitation sampling site, although atmospheric photooxidation was expected to reduce particularly concentrations of non-chlorinated OPs during transport from urban to remote areas in summer months with higher global irradiation. In the SWHT a seasonal trend with decreasing concentrations in summer/autumn is evident for the non-chlorinated OPs due to in-lake degradation but not for the chlorinated OPs. Furthermore, an accumulation of OPs deposited in SWHTs was observed with concentrations often exceeding those observed in wet precipitation. Median concentrations of TCPP (880 ng L −1), TDCP (13 ng L −1) and TBEP (77 ng L −1) at the SWHT were more than twice as high as median concentrations measured at the urban precipitation sampling site (403 ng L −1, 5 ng L −1, and 21 ng L −1 respectively).

House Dust Concentrations of Organophosphate Flame Retardants in Relation to Hormone Levels and Semen Quality Parameters

BackgroundOrganophosphate (OP) compounds, such as tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP), are commonly used as additive flame retardants and plasticizers in a wide range of materials. Although widespread human exposure to OP flame retardants is likely, there is a lack of human and animal data on potential health effects.ObjectiveWe explored relationships of TDCPP and TPP concentrations in house dust with hormone levels and semen quality parameters.MethodsWe analyzed house dust from 50 men recruited through a U.S. infertility clinic for TDCPP and TPP. Relationships with reproductive and thyroid hormone levels, as well as semen quality parameters, were assessed using crude and multivariable linear regression.ResultsTDCPP and TPP were detected in 96% and 98% of samples, respectively, with widely varying concentrations up to 1.8 mg/g. In models adjusted for age and body mass index, an interquartile range (IQR) increase in TDCPP was associated with a 3% [95% confidence interval (CI), −5% to −1%) decline in free thyroxine and a 17% (95% CI, 4–32%) increase in prolactin. There was a suggestive inverse association between TDCPP and free androgen index that became less evident in adjusted models. In the adjusted models, an IQR increase in TPP was associated with a 10% (95% CI, 2–19%) increase in prolactin and a 19% (95% CI, −30% to −5%) decrease in sperm concentration.ConclusionOP flame retardants may be associated with altered hormone levels and decreased semen quality in men. More research on sources and levels of human exposure to OP flame retardants and associated health outcomes are needed.

Organophosphorus Flame Retardants and Plasticizers in Rain and Snow from Middle Germany

AbstractThe role of precipitation as an important source of, and entry pathway for, organophosphates (OPs) into the aquatic environment was investigated. Rainwater and snow samples (53 and 43, respectively) collected between November 2007 and April 2008 from urban and remote areas of middle Germany were analyzed for OPs by gas chromatography‐mass spectrometry (GC‐MS) after solid phase extraction (SPE). The analytes tris(2‐chloroethyl) phosphate (TCEP), tris(2‐chloro‐1‐methylethyl) phosphate (TCPP), tris(1,3‐dichloro‐2‐propyl) phosphate (TDCP), tris(2‐butoxyethyl) phosphate (TBEP), tri‐iso‐butyl phosphate (TiBP), and tri‐n‐butyl phosphate (TnBP) were detected in almost all rain and snow samples. TCPP was the most abundant chlorinated alkyl‐phosphate ester in urban rainwater, with concentrations ranging from 46 to 2659 ng L–1. In general, concentrations of OPs in urban rainwater were 3 to 4 times higher than those at background monitoring stations, e. g., Schmücke and Thuringian Forest. Variable concentrations of chlorinated flame retardants were found in precipitation, but their occurrence was not correlated with air temperature. The results of the study indicate that volatilization of OPs from objects protected by flame retardants, including vehicles and buildings, causes these compounds to reach the aquatic environment via washout from the atmosphere, despite their reported short atmospheric half‐lives (&lt; 24 h).