Assessment of human dermal absorption of flame retardant additives in polyethylene and polypropylene microplastics using 3D human skin equivalent models.

To overcome ethical and technical challenges impeding the study of human dermal uptake of chemical additives present in microplastics (MPs), we employed 3D human skin equivalent (3D-HSE) models to provide first insights into the dermal bioavailability of polybrominated diphenyl ether (PBDEs) present in MPs; and evaluated different factors influencing human percutaneous absorption of PBDEs under real-life exposure scenario. PBDEs were bioavailable to varying degrees (up to 8 % of the exposure dose) and percutaneous permeation was evident, albeit at low levels (≤0.1 % of the exposure dose). While the polymer type influenced the release of PBDEs from the studied MPs to the skin, the polymer type was less important in driving the percutaneous absorption of PBDEs. The absorbed fraction of PBDEs was strongly correlated (r2 = 0.88) with their water solubility, while the dermal permeation coefficient Papp of PBDEs showed strong association with their molecular weight and logKOW. More sweaty skin resulted in higher bioavailability of PBDEs from dermal contact with MPs than dry skin. Overall, percutaneous absorption of PBDEs upon skin contact with MPs was evident, highlighting, for the first time, the potential significance of the dermal pathway as an important route of human exposure to toxic additive chemicals in MPs.

Organophosphate triesters and their diester degradation products in the atmosphere-A critical review.

Organophosphate triesters (tri-OPEs) have found substantial use as plasticizers and flame retardants in commercial and industrial products. Despite upcoming potential restrictions on use of OPEs, widespread environmental contamination is likely for the foreseeable future. Organophosphate diesters (di-OPEs) are known biotic or abiotic degradation products of tri-OPEs. In addition, direct use of di-OPEs as commercial products also contributes to their presence in the atmosphere. We review the available data on contamination with tri-OPEs and di-OPEs in both indoor and outdoor air. Concentrations of tri-OPEs in indoor air exceed those in outdoor air. The widespread discovery of tri-OPE traces in polar regions and oceans is noteworthy and is evidence that they undergo long-range transport. There are only two studies on di-OPEs in outdoor air and no studies on di-OPEs in indoor air until now. Current research on di-OPEs in indoor and outdoor air is urgently needed, especially in countries with potentially high exposure to di-OPEs such as the UK and the US. Di-OPE concentrations are higher at e-waste dismantling areas than at surrounding area. We also summarise the methods employed for sampling and analysis of OPEs in the atmosphere and assess the relative contribution to atmospheric concentrations of di-OPEs made by environmental degradation of triesters, compared to the presence of diesters as by-products in commercial triester products. Finally, we identify shortcomings of current research and provide suggestions for future research.

Interspecies comparison of metabolism of two novel prototype PFAS.

As a result of proposed global restrictions and regulations on current-use per-and polyfluoroalkyl substances (PFAS), research on possible alternatives is highly required. In this study, phase I in vitro metabolism of two novel prototype PFAS in human and rat was investigated. These prototype chemicals are intended to be safer-by-design and expected to mineralize completely, and thus be less persistent in the environment compared to the PFAS available on the market. Following incubation with rat liver S9 (RL-S9) fractions, two main metabolites per initial substance were produced, namely an alcohol and a short-chain carboxylic acid. While with human liver S9 (HL-S9) fractions, only the short-chain carboxylic acid was detected. Beyond these major metabolites, two and five additional metabolites were identified at very low levels by non-targeted screening for the ether- and thioether-linked prototype chemicals, respectively. Overall, complete mineralization during the in vitro hepatic metabolism of these novel PFAS by HL-S9 and RL-S9 fractions was not observed. The reaction kinetics of the surfactants was determined by using the metabolite formation, rather than the substrate depletion approach. With rat liver enzymes, the formation rates of primary metabolite alcohols were at least two orders of magnitude higher than those of secondary metabolite carboxylic acids. When incubating with human liver enzymes, the formation rates of single metabolite carboxylic acids, were similar or smaller than those experienced in rat. It also indicates that the overall metabolic rate and clearance of surfactants are significantly higher in rat liver than in human liver. The maximum formation rate of the thioether congener exceeded 10-fold that of the ether in humans but were similar in rats. Overall, the results suggest that metabolism of the prototype chemicals followed a similar trend to those reported in studies of fluorotelomer alcohols.

Characterization and dermal bioaccessibility of residual- and listed PFAS ingredients in cosmetic products.

As a large group of chemicals with diverse properties, per- and polyfluoroalkyl substances (PFAS) have found extensive application throughout consumer products, including cosmetics. Little is known about the importance of dermal uptake as a human exposure pathway for PFAS. Here we investigate a suite of listed-ingredient and residual PFAS in cosmetic products, along with their dermal bioaccessibility using in vitro incubations with artificial sweat. Concentrations of volatile listed ingredients (including cyclic perfluorinated alkanes, perfluorinated ethers, and polyfluorinated silanes) in three products ranged from 876-1323 µg g-1, while polar listed ingredients (i.e., polyfluoroalkyl phosphate esters [PAPs]) in a single product occurred at up to 2427 µg g-1 (6 : 2/6 : 2 diPAP)). Residual perfluoroalkyl carboxylic acids (PFCAs) were also measured at concentrations ranging from 0.02-29 µg g-1. When listed ingredients were included, our targeted analysis accounted for up to 103% of the total fluorine, while highlighting ambiguous and/or incorrect International Nomenclature of Cosmetic Ingredient (INCI) names used in several products. Bioaccessibility experiments revealed that residual PFCAs readily partitioned to artificial sweat (bioaccessible fractions ranging from 43-76% for detectable substances) while listed ingredients (i.e., PAPs and neutral/volatile PFAS) displayed negligible partitioning. This work provides new insight into the occurrence of PFAS in cosmetic products, while furthering our understanding on their mechanisms of dermal uptake.

Dermal uptake of chlorinated organophosphate flame retardants via contact with furniture fabrics; implications for human exposure.

The chlorinated organophosphate flame retardants (Cl-PFRs): tris-(2-chloroethyl)-phosphate (TCEP), tris-(1-chloro-2-propyl)-phosphate (TCIPP) and tris-(1,3-dichloropropyl)-phosphate (TDCIPP), have been widely used in upholstered furniture despite their carcinogenic potential. Although Cl-PFRs are mainly added to furniture foam, they are present in the fabrics likely due to migration from the foam. While several studies have assessed human exposure to Cl-PFRs via different pathways, no information exists on dermal uptake of these chemicals through contact with fabrics. In the current study, dermal absorption of TCEP, TCIPP and TDCIPP from 3 UK domestic furniture fabrics was experimentally assessed for the first time using in vitro 3D-human skin equivalents (EpiSkin™) under different real-life exposure scenarios. Results revealed all 3 target Cl-PFRs were dermally bioavailable to varying degrees (3.5%-25.9% of exposure dose) following 24 h contact with the studied fabrics. Estimated permeability coefficients (KP, cm h-1) showed TCEP had the highest percutaneous penetration potential followed by TCIPP, then TDCIPP. Further investigation revealed human dermal uptake of Cl-PFRs can be influenced by several factors including: the specific physicochemical properties of the compound, the type of exposure matrix, the exposure dose and the degree of skin hydration at the point of contact. Exposure assessment revealed UK adults and toddlers can be exposed to 20.4 and 14.1 ng TCIPP/kg bw/day via contact with furniture fabrics in summer, which is higher than international average exposures via inhalation and dust ingestion for adults and dietary exposure for toddlers. Therefore, risk assessment studies for Cl-PFRs and future replacements should consider dermal contact with consumer products (e.g. furniture fabrics) as a potential significant human exposure pathway.

The Time Machine framework: monitoring and prediction of biodiversity loss.

Transdisciplinary solutions are needed to achieve the sustainability of ecosystem services for future generations. We propose a framework to identify the causes of ecosystem function loss and to forecast the future of ecosystem services under different climate and pollution scenarios. The framework (i) applies an artificial intelligence (AI) time-series analysis to identify relationships among environmental change, biodiversity dynamics and ecosystem functions; (ii) validates relationships between loss of biodiversity and environmental change in fabricated ecosystems; and (iii) forecasts the likely future of ecosystem services and their socioeconomic impact under different pollution and climate scenarios. We illustrate the framework by applying it to watersheds, and provide system-level approaches that enable natural capital restoration by associating multidecadal biodiversity changes to chemical pollution.

Concentrations of halogenated flame retardants and polychlorinated biphenyls in house dust from Lagos, Nigeria.

Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and hexabromocyclododecane (HBCDD) are regulated under the Stockholm Convention of the United Nations' Environment Programme; with similar concerns emerging about alternative halogenated flame retardants (alt-HFRs), the use of which is increasing as replacements for PBDEs and HBCDD. While the presence in indoor dust of PCBs, PBDEs, and HBCDDs has been reported previously in a few African locations including Lagos, Nigeria, we are unaware of similar data for alt-HFRs. The present study thus aimed to provide the first information on alt-HFRs in indoor dust in sub-Saharan Africa, and to evaluate the impact of restrictions on the use of PBDEs, HBCDD, and PCBs on their concentrations in house dust in Lagos, Nigeria. Concentrations of ∑8PBDEs, ∑HBCDDs, ∑7alt-HFRs, and ∑8PCBs in 15 samples of dust from homes in Lagos, Nigeria were found to be: 43-810 (median = 300) ng g-1,

A meta-analysis of factors influencing concentrations of brominated flame retardants and organophosphate esters in indoor dust.

Current assessments of human exposure to flame retardants (FRs) via dust ingestion rely on measurements of FR concentrations in dust samples collected at specific points in time and space. Such exposure assessments are rendered further uncertain by the possibility of within-room and within-building spatial and temporal variability, differences in dust particle size fraction analysed, as well as differences in dust sampling approach. A meta-analysis of peer-reviewed data was undertaken to evaluate the impact of these factors on reported concentrations of brominated flame retardants (BFRs) and organophosphate esters (OPEs) in dust and subsequent human exposure estimates. Except for a few cases, concentrations of FRs in elevated surface dust (ESD) exceeded significantly those in floor dust (FD). The implications of this for exposure assessment are not entirely clear. However, they imply that analysing FD only will underestimate exposure for adults who likely rarely ingest floor dust, while analysing ESD only would overestimate exposure for toddlers who likely rarely ingest elevated surface dust. Considerable within-building spatial variability was observed with no specific trend between concentrations of either BFRs or OPEs in living rooms and bedrooms in the same homes, implying that exposure assessments based solely on sampling one room are uncertain. Substantial differences in FR concentrations were observed in different particle size fractions of dust. This is likely partly attributable to the presence of abraded polymer particles/fibres with high FR concentrations in larger particle size fractions. This has implications for exposure assessment as adherence to skin and subsequent FR uptake via ingestion and dermal sorption varies with particle size. Analysing dust samples obtained from a householder vacuum cleaner (HHVC) compared with researcher collected dust (RCD) will underestimate human exposure to the most of studied contaminants. This is likely due to the losses of volatile FRs from HHVC dust over the extended period such dust spends in the dust bag. Temporal variability in FR concentrations is apparent during month-to-month or seasonal monitoring, with such variability likely due more to changes in room contents rather than seasonal temperature variation.

Exploring variations of hexabromocyclododecane concentrations in riverine sediments along the River Medway, UK.

Surface riverine sediment samples were collected along the course of the River Medway, UK, between Yalding and the mouth of the estuary at 40 different sites. The samples were then analysed for hexabromocyclododecane (HBCDD) concentrations using a liquid chromatography system coupled to a high-resolution, accurate mass Orbitrap™ mass spectrometer. After normalisation to the sediment organic carbon (OC) content, average ΣHBCDD was 270 ng g-1 OC with a maximum concentration of 1006 ng g-1 OC. Spatial trend analysis revealed that industrial and residential land uses have significantly influenced HBCDD concentrations and profiles in riverine sediments. Higher concentrations of ΣHBCDD were found in sites near construction and maritime port locations, and these included freight ports, new builds and demolition sites. The HBCDD isomer profile reflected that of the commercial mixture with a comparatively high γ-HBCDD to α-HBCDD and ß-HBCDD. The isomer profiles of sites located near construction activities indicate recent pollution events, with increased γ-HBCDD and decreased α-HBCDD compared to the study area's average profile. HBCDD isomer concentrations also indicated that the non-tidal portions of the river caused by locks showed a profile that was typical of older HBCDD contamination, indicating a possible sediment and HBCDD trap.

Phasing-out of legacy brominated flame retardants: The UNEP Stockholm Convention and other legislative action worldwide.

Due to their toxicity and persistence, several families of brominated flame retardants (BFRs) have been listed as persistent organic pollutants (POPs) in the Stockholm Convention, a multilateral treaty overseen by the United Nations Environment Programme. This treaty mandates that parties who have signed must take administrative and legislative actions to prevent the environmental impacts that POPs pose, both within their jurisdictions and in the global environment. The specific BFRs listed in the Stockholm Convention are Polybrominated Diphenyl Ethers (PBDEs), Hexabromocyclododecane (HBCDD), and Hexabromobiphenyl (HBB), chemicals which must therefore be heavily restricted within the jurisdictions of the signatories. As an example, within the EU, hexabromobiphenyl (HBB), the PBDE commercial mixtures, and HBCDD are almost entirely prohibited in terms of both production and use in commercial goods. Waste articles containing excess concentrations of these BFRs are similarly restricted and must be disposed of in a manner that destroys or irreversible transforms the BFR in question. In some cases, specific exemptions for these limits are defined by the Convention for certain parties: for example, Penta- and Octa-BDE can be present in waste materials for recycling until 2030, while Deca-BDE can be applied to some aviation and automotive applications until 2036. However, in such cases, very specific criteria and guidelines apply for their use and/or production. Worldwide, China, Japan, India, and the United States of America have made significant advances in the regulation of POPs, in line with the provisions of the Stockholm Convention. China has established concentration limits for Penta- and Octa-BDEs in electronic goods. It is also currently availing of an exemption to allow for the use of HBCDD and has not yet ratified the Convention with regards to Deca-BDE. Japan meanwhile has classified HBB and Penta-/Octa-BDE compounds as Class I Specified Chemical Substances which virtually prohibits the manufacture, import, and use of these chemicals in all applications. India has banned the manufacture, trade, import, and use of HBB, HBCDD and some PBDEs, and has established concentration limits for all PBDEs in certain electrical goods. Finally, the United States has no federal mandate for the restriction of POPs and has not ratified the annexes to the Convention requiring them to do so. However, thirteen states have implemented their own state-wide concentration limits on a variety of flame retarding chemicals in various commercial applications. Though these limits worldwide are a very positive step for the removal of POP-BFRs from the environment, the increased use of replacement flame retardants renders such legislation only partially effective. The lack of effective screening mechanisms in waste management facilities means that BFR-treated plastics can be inadvertently recycled and remain in circulation. The rise in the use of novel BFRs (NBFRs) can furthermore hinder screening methods currently being developed and the additives themselves may pose similar issues to their predecessors owing to their similar chemical properties. Thus, restrictions on current BFRs will result in the use of new flame retardants, which may in turn be banned and replaced once again. Further research into and development of methods to screen for hazardous chemicals in end of life materials is therefore of the utmost importance. This must be coupled with pro-active legislation that eliminates the need for using such persistent and potentially harmful chemicals in the future.

A single run, rapid polarity switching method for determination of 30 pharmaceuticals and personal care products in waste water using Q-Exactive Orbitrap high resolution accurate mass spectrometry.

The analytical capability of the UPLC-Q Exactive™ Orbitrap MS was exploited for simultaneous determination of 30 acidic and basic PPCPs in a single run, using rapid polarity switching of the electrospray ionisation source. Full scan MS mode at resolution of 35,000 FWHM, Automatic gain control (AGC) target of 1E6 ions at injection time of 50 ms provided the optimum parameters for high sensitivity, together with sufficient data points per peak (≥15) for improved reproducibility. In addition to chromatographic retention times, method selectivity was achieved via applying high resolution accurate mass with low mass tolerance filter (<5 ppm) for identification of each target compound. Six-point linear calibration curves (R2 > 0.95) were established for all target analytes over a concentration range of 1-1500 ng/ml. Good results were obtained for method accuracy (% recovery = 76-104%), inter- and intra-day precision (relative standard deviation <15%) at 3 concentration levels. Instrumental detection and quantification limits ranged from (0.02-1.21 ng/ml) and (0.07-4.05 ng/ml), respectively. While optimised MS/MS analysis through parallel reaction monitoring (PRM) mode provided slightly higher sensitivity, Full scan MS mode allowed for higher mass resolution (selectivity), more data points per peak (reproducibility) and more importantly, the potential for post-acquisition screening of non-target compounds. Following solid phase extraction (SPE) of target analytes, the method was successfully applied to provide first data on PPCPs occurrence in effluent and surface water samples (n = 10) from Egypt. Moreover, screening for non-target compounds revealed the presence of bisphenol A, which was further confirmed via matching with an authentic standard. Overall, this study provides first insight into the high analytical capabilities of the Q-Exactive™ Orbitrap platform for both targeted/non-targeted analysis of PPCPs in environmental matrices.

Biotransformation of the Flame Retardant 1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH) in Vitro by Human Liver Microsomes.

The technical mixture of 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH or DBE-DBCH) and the pure ß-TBECH isomer were subjected to in vitro biotransformation by human liver microsomes (HLM). After 60 min of incubation, 5 potential metabolites of TBECH were identified in microsomal assays of both the TBECH mixture and ß-TBECH using ultraperformance liquid chromatography-Q-Exactive Orbitrap mass spectrometry. These include mono- and dihydroxylated TBECH and mono- and dihydroxylated TriBECH as well as an α-oxidation metabolite bromo-(1,2-dibromocyclohexyl)-acetic acid. Our results indicate potential hepatic biotransformation of TBECH via cyctochrome P450-catalyzed hydroxylation, debromination, and α-oxidation. Kinetic studies revealed that the formation of monohydroxy-TBECH, dihydroxy-TBECH, and monohydroxy-TriBECH were best fitted to a Michaelis-Menten enzyme kinetic model. Respective estimated Vmax values (maximum metabolic rate) for these metabolites were 11.8 ± 4, 0.6 ± 0.1, and 10.1 ± 0.8 pmol min-1 mg protein-1 in TBECH mixture and 4992 ± 1340, 14.1 ± 4.9, and 66.1 ± 7.3 pmol min-1 mg protein-1 in ß-TBECH. This indicates monohydroxy-TBECH as the major metabolite of TBECH by in vitro HLM-based assay. The estimated in vitro intrinsic clearance (Clint) of TBECH mixture was slower (P < 0.05) than that of pure ß-TBECH. While the formation of monohydroxy-TBECH may reduce the bioaccumulation potential and provide a useful biomarker for monitoring TBECH exposure, further studies are required to fully understand the levels and toxicological implications of the identified metabolites.

Emerging and legacy flame retardants in UK human milk and food suggest slow response to restrictions on use of PBDEs and HBCDD.

The legacy flame retardants (LFRs) polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD), together with six emerging flame retardants (EFRs) were measured in United Kingdom (UK) human milk collected in 2010 (n=25) and 2014-15 (n=10). These data are the first report of the presence of EFRs in UK human milk. The most abundant EFR was ß-tetrabromoethylcyclohexane (DBE-DBCH) (average=2.5ng/g lw; geometric mean=1.5ng/g lw), which is comparable to the concentrations of the most abundant LFRs i.e. BDE 47 and α-HBCDD at 2.8 and 2.1ng/g lw, respectively (geometric mean=2.1 and 1.7). The estimated median dietary intake of ΣEFRs by UK nursing infants was 18ng/kg bw/day. EFRs were also measured in UK foodstuffs with ß-DBE-DBCH again the predominant compound detected, accounting - on average - for 64.5±23.4% of ΣEFRs. Average estimated dietary intakes of ∑EFRs in the UK were 89 and 26ng/day (1.3 and 2.6ng/body weight/day) for adults and toddlers, respectively. Concentrations of Σtri-hexa BDEs in our UK food samples exceeded those reported in UK samples from the same food categories collected in 2003-04 and 2006. Despite this and our recent report elsewhere of significant temporal declines in concentrations of BDE 209 in UK indoor dust (p<0.05) and HBCDDs in UK indoor dust and air (p<0.001), no significant temporal differences (p>0.05) were observed between concentrations of Σtri-hexa BDEs, BDE 209 and HBCDDs in human milk sampled in 2010 and those obtained in 2014-15. UK adult body burdens for EFRs were predicted via inhalation, diet and dust ingestion using a simple pharmacokinetic model. The predicted EFR body burdens compared well with observed concentrations in human milk.

Levels and profiles of organohalogenated contaminants in human blood from Egypt.

Concentrations of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and some organochlorine pesticides (OCPs) were determined in serum of Egyptian colorectal cancer patients (n = 35) and compared to a healthy control group (n = 32). p,p'-DDE (the major metabolite of DDT) was the most frequently detected contaminant with the highest concentration (median = 131 ng/g lw) in all studied serum samples. BDE-209 was the least frequently detected contaminant with a median concentration <0.3 ng/g lw. The contamination profile in patients and controls was almost identical with p,p'-DDE showing the highest median contribution (77%) and oxychlordane the lowest (1%). The low p,p'-DDT/p,p'-DDE ratio (3.7%) in serum implies bioaccumulation and past exposure to DDT (c.f. recent and ongoing intake). Statistical analysis revealed no significant differences (P > 0.05) between the levels of target contaminants in serum of patients and the control group. Gender, age and body mass index (BMI) were investigated as potential factors influencing serum contaminant levels. ΣDDT, hexachlorobenzene and pentachlorophenol concentrations showed significant positive associations with age and/or BMI of the participants. Comparison with other countries revealed concentrations of PBDEs and PCBs in Egyptian serum among the lowest reported worldwide.

Environmental occurrence, analysis and human exposure to the flame retardant tetrabromobisphenol-A (TBBP-A)-A review.

TBBP-A is a high production volume chemical applied widely as a flame retardant in printed circuit boards. Recent studies have raised concern over potential harmful implications of TBBP-A exposure in human and wildlife, leading to its classification under group 2A "Probably carcinogenic to humans" by the International Agency for Research on Cancer. This article provides a comprehensive review of the available literature on TBBP-A analysis, environmental levels and human exposure. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been identified as the method of choice for robust, accurate and sensitive analysis of TBBP-A in different matrices. TBBP-A has been detected in almost all environmental compartments all over the world, rendering it a ubiquitous contaminant. Human exposure studies revealed dust ingestion and diet as the major pathways of TBBP-A exposure in the general population. Toddlers are likely to be more exposed than adults via accidental indoor dust ingestion. Moreover, exposure to TBBP-A may occur prenatally and via breast milk. There are no current restrictions on the production of TBBP-A in the EU or worldwide. However, more research is required to characterise human exposure to TBBP-A in and around production facilities, as well as in e-waste recycling regions.

Human dermal absorption of chlorinated organophosphate flame retardants; implications for human exposure.

Tris-2-chloroethyl phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP) and tris-1,3-dichloropropyl phosphate (TDCIPP) are organophosphate flame retardants (PFRs) widely applied in a plethora of consumer products despite their carcinogenic potential. Human dermal absorption of these PFRs is investigated for the first time using human ex vivo skin and EPISKIN™ models. Results of human ex vivo skin experiments revealed 28%, 25% and 13% absorption of the applied dose (500 ng/cm(2), finite dose) of TCEP, TCIPP and TDCIPP, respectively after 24h exposure. The EPISKIN™ model showed enhanced permeability values (i.e. weaker barrier), that were respectively 16%, 11% and 9% for TCEP, TCIPP and TDCIPP compared to human ex vivo skin. However, this difference was not significant (P>0.05). Estimated permeability constants (Kp, cm/h) showed a significant negative correlation with log Kow for the studied contaminants. The effect of hand-washing on dermal absorption of PFRs was investigated. Washing reduced overall dermal absorption, albeit to varying degrees depending on the physicochemical properties of the target PFRs. Moreover, slight variations of the absorbed dose were observed upon changing the dosing solution from acetone to 20% Tween 80 in water, indicating the potential influence of the dose vehicle on the dermal absorption of PFRs. Finally, estimated dermal uptake of the studied PFRs via contact with indoor dust was higher in UK toddlers (median ΣPFRs=36 ng/kg bw day) than adults (median ΣPFRs=4 ng/kg bw day). More research is required to fully elucidate the toxicological implications of such exposure.

Advances in Instrumental Analysis of Brominated Flame Retardants: Current Status and Future Perspectives.

This review aims to highlight the recent advances and methodological improvements in instrumental techniques applied for the analysis of different brominated flame retardants (BFRs). The literature search strategy was based on the recent analytical reviews published on BFRs. The main selection criteria involved the successful development and application of analytical methods for determination of the target compounds in various environmental matrices. Different factors affecting chromatographic separation and mass spectrometric detection of brominated analytes were evaluated and discussed. Techniques using advanced instrumentation to achieve outstanding results in quantification of different BFRs and their metabolites/degradation products were highlighted. Finally, research gaps in the field of BFR analysis were identified and recommendations for future research were proposed.