Ecotoxicity of emerging halogenated flame retardants

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Ecotoxicity of emerging halogenated flame retardants
Mario Ortega-Olvera, Alejandro Mejía-García, Hariz Islas-Flores, Jose María Dolores Hernández-Navarro, Leobardo Manuel Gómez-Oliván∗ Laboratorio de Toxicologı´a Ambiental, Facultad de Quı´mica, Universidad Auto´noma del Estado de M
exico, Toluca, Estado de M
exico, M
exico ∗ Corresponding author: e-mail address: [email protected]

Contents 1. Introduction 2. Occurrence and ecotoxicity of HFR in air 3. Occurrence and ecotoxicity of HFR in soils 4. Ecotoxicity of HFR in water 5. Conclusions References

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1. Introduction For many years, FR have been used to prevent fires [1] and being used around the world as additives in buildings, transportation, electronics and consumer products, coupled with the increasing demand for fire safety resulting in a wide variety of FR being marketed in large volumes annually [2]. From a chemical management perspective, FR can be classified in regulated, emerging and novel compounds [3]. And within these, the halogenated flame retardants (HFR) has been widely studied in several countries in addition to being subjects of regulatory scrutiny for decades due to their resistance to environmental degradation, their toxic and bioaccumulative properties as well as their potential for long-range transport to remote regions [4–7]. According to its structure, halogenated FRs can be of three classes: aliphatic, cycloaliphatic and aromatic [1,8,9]. On the other hand, also are usually based on chlorine and bromine. Polychlorinated biphenyls (PCBs) are historical contaminants that persist at relatively high concentrations in Comprehensive Analytical Chemistry ISSN 0166-526X https://doi.org/10.1016/bs.coac.2019.11.004

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2019 Elsevier B.V. All rights reserved.

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wildlife [10], while the polybrominated diphenyl ethers (PBDEs) are the most extensively studied group of FRs that have proven to be ubiquitous environmental contaminants with the ability to bioaccumulate in the tissues of wildlife and humans [11] due to their efficiency and because at high temperatures, the decomposition products of brominated compounds are less volatile than are those derived from chlorinated compounds due to its weight [9]. PBDEs constitute a major and most concerning group of brominated FRs (BFRs) because of their large-scale use since the 1970s, and as mentioned above also due to their bioaccumulation capacity and toxic properties. It should be noted that BFRs have been regulated over the past decade, an example are those included in the Annex A of the “Stockholm Convention on Persistent Organic Pollutants” [12–14] specifically the main components of commercial octabromodiphenyl ether (octaBDE), pentabromodiphenyl ether (pentaBDE), decabromodiphenyl ether (decaBDE), hexabromobiphenyl (HBB) and hexabromocyclododecane (HBCD), while octaBDE, pentaBDE as well as HBCD are listed as priority substances under the EU Water Framework Directive (2000/60/EC) leading to an obligation for EU countries to monitor these compounds in aquatic biota on an EU-wide scale. For this reason the production of PBDEs has either ceased or has been regulated in many countries; however, these contaminants are considered as emerging substances, identified in significant concentrations in various ecosystems worldwide [10]. After PBDE restrictions, alternative FRs have been introduced to the industrial market. Some emerging BFRs are hexabromobenzene (HBB), pentabromoethyl benzene (PBEB) or decabromodiphenyl ethane (DBDPE). Moreover, the family of halogenated norbornenes are part of chlorinated FRs, including Dechlorane 602 (Dec 602), Dechlorane 603 (Dec 603), Dechlorane 604 (Dec 604) and Dechlorane Plus (DP). They have also proved their ubiquity as they have been found in different environmental and biological samples around the world [15].

2. Occurrence and ecotoxicity of HFR in air Air pollution is defined as the introduction by man, directly or indirectly into the atmosphere and enclosed spaces of hazardous substances presenting risks to health and ecosystems [16]. This type of pollution contributes to serious diseases of respiratory, cardiovascular, and reproductive systems [17–19].

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Ecotoxicity of emerging halogenated flame retardants

One of the most commonly used bioindicators are birds, since have species-specific migratory and dietary habits. Resident birds are good indicators of local contamination, whereas migratory birds may be useful in examining broader scale scenarios. Specifically speaking of HFR, the examination of piscivorous and terrestrial-feeding birds may reveal differences in PBDE transport and fate between aquatic and terrestrial ecosystems, also, study of addled eggs provides a non-destructive way to investigate contamination and are also suitable for long-term monitoring purposes [20]. In birds, FR causes various behavioural, neurological and physiological abnormalities that can affect the reproduction and health of species and ultimately could affect population dynamics [21–23]. One table with the findings found is presented in Table 1. Table 1 Biomarkers and toxicity studies of HRF in birds. FR class Species Effects

Reference

PBDE

Baltic Reported that PBDE concentrations [24] guillemot eggs peaked in the late 1980s (1300 ng/g lw), and then decreased to below 100 ng/g lw in 2001

PBDE

Swedish peregrine falcon (Falco peregrinus) eggs

Reported concentrations of 2200 ng/g lw in the northern and 2700 in the southern populations BDE-209 concentrations were 80 and 86 ng/g lw in the two populations

PBDE

Fulmar (Fulmarus glacialis)

Eggs collected from the Faroe Islands [26] exhibited similar concentrations (21 ng/g lw) as guillemots from the same region. BDE-209 was detectable in the majority of adult fulmar muscle tissues, at concentrations of up to 62 ng/g lw

PBDE

Norwegian ospreys (P. haliaetus)

Found concentrations of 1100 ng/g lw in eggs

White-tailed sea eagles (Haliaeetus albicilla) eggs

Found concentrations of 1900 ng/g lw in eggs

[25]

[27]

Continued

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Table 1 Biomarkers and toxicity studies of HRF in birds.—cont’d FR class Species Effects

Reference

PBDE

South Greenland peregrine falcon eggs

Reported a concentration of [28] 1900 ng/g lw for PBDEs and 11 ng/g lw for BDE-209

PBDE

American kestrel (Falco sparverius)

Exposure to pentaBDE (DE-71) in ovo during development induced changes in thyroid, vitamin A, glutathione homeostasis, oxidative stress, and immunomodulatory changes

PBDE

American kestrel (Falco sparverius)

DE-71: affected the growth of kestrel [30] nestlings, were larger in weight, bones and feathers, which may be detrimental to their bone structure and represent an excessive energy sink BDE-100 was associated with size, weight gain and food consumption, and was suggested to be most influential on nestling growth BDE-153 and -183 may be related to longer bones BDE-99 was associated with longer feathers

PBDE

Common buzzard (Buteo buteo) Kestrel (Falco tinnunculus) Sparrowhawk (Accipiter nisus) Barn owl (Tyto alba) Grey heron (Ardea cin
erea) Great crested grebe (Podiceps cristatus)

[31] PCBs were the predominant compounds with highest concentrations in the liver of barn owl (Tyto alba) and sparrowhawk (Accipiter nisus). Sparrowhawks had the highest levels of PBDEs. BDE-47 was the most abundant congener in heron (Ardea cinerea) and grebe (Podiceps cristatus), while BDE-47, 99 and 153 were equally important in the terrestrial species. BDE-183 and BDE-209 were only measured in the terrestrial birds

[29]

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Ecotoxicity of emerging halogenated flame retardants

Table 1 Biomarkers and toxicity studies of HRF in birds.—cont’d FR class Species Effects

Reference

PBDE

Herring gulls (Larus argentatus)

R-HBCD concentrations ranged [32] from 2.1 to 20 ng/g (wet weight (ww)). Mother herring gulls are exposed to several, current-use flame retardants via their diet, and in ovo transfer occurred to their eggs. Given to the aquatic diet of herring gull, this suggests that there are non-PBDE BFRs present in the gull-associated aquatic food web

PBDE

European starlings (Sturnus vulgaris)

PentaBDE mixture exposed group [33] laid eggs compared to the control group, although the difference was not significant, but, the eggs laid by exposed females were significantly greater in weight and volume

PBDE

Wild osprey (Pandion haliaetus)

Concentrations in the vicinity of 1 μg/g wet weight of PBDEs may reduce osprey reproductive performance

PBDE

Peregrine falcon (Falco peregrinus)

Reported a significant negative [35] correlation between average brood size for individual female peregrine P falcons and PBDE burden in eggs

PBDE and Peregrine polychlorinated falcon (Falco biphenyls peregrinus)

Urban nestlings had higher BDE-99: [36] BDE-153 ratios, higher BDE-183 proportions, and the only detectable HBCD concentrations, suggesting greater and more localized exposure to HBCD and PBDEs derived from octaBDEs. Spatial patterns reflected differences in diet, local contaminant sources, and/or atmospheric deposition

PBDE

Reported sex-specific effects in the [37] thyroid system responses to the BTBPE exposures, with type 2 deiodinase (D2) activity decreasing at higher doses in female, but not in male hatchlings, suggesting that females may be more sensitive to BTBPE

American kestrel (Falco sparverius)

[34]

Continued

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Table 1 Biomarkers and toxicity studies of HRF in birds.—cont’d FR class Species Effects

PBDE and dechloranes

Grey heron (Ardea cinerea) Purple heron (Ardea purpurea) Blackcrowned night heron (Nycticorax) Western marsh harrier (Circus aeruginosus)

Reference

[38] PBDEs and dechloranes were detected in bird eggs at levels ranging from 22 to 5167 ng/g lw and from nd to 132 ng/g lw, respectively. PBDE contamination was related to the pentaBDE formulation, with BDE47, -99, -100 and -153 as the most abundant PBDE congeners. For dechloranes, Dec 602 was the most abundant compound

3. Occurrence and ecotoxicity of HFR in soils Recent information has shown the presence of brominated flame retardants (BFRs) in various concentrations in the air, water, soil, sewage and sediments, even away from the places where they were manufactured. In addition, traces of BFR have been found in plants, wildlife and even in human samples [39]. The analysis of concentrations of flame retardants in the soil, besides showing concern about the toxic effects they can generate in the environment, is of great help in determining its origin. For example, the rates of brominated flame retardants such as TBC, HBDC and TBBPA showed a positive correlation, in different soil samples, with significative higher levels at waste discharge sites and industrial areas, which indicates a common source [40]. In addition, human activities also play an important role in the concentration of organophosphorus compounds (OP) present in sediments [41]. Flame retardants such as hexabromocyclododecanes (HBCD) and tetrabromobisphenol A (TBBPA) are raising concern due to their potential persistence, bioaccumulation and toxicity. Halogenated flame retardants have a high sorption affinity to particles, which makes soils and sediments important sinks [42]. A study by Tang et al. [42a] demonstrated the presence of tris(2,3dibromopropyl) isocyanurate (TBC), a brominated flame retardant, in soil samples, being in relatively low concentrations that vary from below of the detection limits (0.024 ng/g) to 16.4 ng/g on a dry weight (d.w.) basis

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with an average level of 0.95 ng/g d.w. Similarly, HBCD levels ranged below the detection limits (0.020 ng/g) to 102.6 ng/g d.w., with an average level of 15.8 ng/g d.w.; while for TBBPA, the concentration varied from below the detection limits (0.025 ng/g) to 78.6 ng/g d.w. with the average level of 9.17 ng/g d.w. [40]. Another group of flame retardant of great interest corresponds to organophosphorus compounds (OP). Their concentrations and distribution were investigated in 28 sediment samples collected from Taihu Lake, China; the total concentrations of organophosphorus flame retardants (OPFR) ranged from 3.38 to 14.25 mg/kg; tris(1,3-dichloro-2-propyl) phosphate (TDCPP) was the main compound. Other retardants such as TCPP (tris(2chloroisopropyl) phosphate), TCEP (tris(2-chloroethyl) phosphate) and TBEP (tris(2-butoxyethyl) phosphate) were dominant, with concentrations ranging from below the limit of quantification at 2.27, 0.62–3.17 and 1.03–5.00 mg/kg, respectively [41]. Derived from anthropogenic activities, compounds with flame retardant activity have been present in the environment for decades, as demonstrated by Qiu and collaborators, who analysed the concentrations of DP (Dechlorane Plus), a highly chlorinated flame retardant, in sediment samples from the central basin of Lake Ontario, Canada, showing a rapid increase from the mid-1970s that reached its maximum concentration (310 ng/g d.w.) in the mid-1990s [43]. On the other hand, the distribution of the principal PBDEs, DP and TBPH isomers that are gradually being eliminated in China, were correlated with an index based on the population density of areas with high use and waste of products containing FR; however, high concentrations of some NBFR (new brominated flame retardants) were observed in industrialized regions and in FR manufacturing plants [44]. Retardants such as diphenyl polybrominated ethers (PBDE) and 1,2-bis(2,4,6-tribromophenoxy) ethane (TBE) were found in surface sediment samples at concentrations of 2.8 and 6.7 ng/g, respectively; exceeding reported values for combined brominated flame retardants [43]. Decabromodiphenylethane (DBDPE) was the most abundant flame retardant found in 159 soil samples from 30 in the background forested mountains sites in China, being in concentrations ranging from 25–18,000 to 5–13,000 pg/g, followed by BDE-209, which was found in maximum concentrations of 5900 and 2400 pg/g (depending on the geographical distribution of the sample), demonstrating that the distributions of FR are mainly controlled by its site of origin [44]. There are few studies related to the evaluation of the toxic effects of flame retardants in soil samples. Sverdrup and colleagues evaluated the toxic

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effects (at sublethal toxicity level) on soil nitrifying bacteria, Trifolium pratense (appearance of seeds and growth of red clover) and Enchytraeus crypticus (soil invertebrate), caused by three of the most commonly used flame retardants [42]. Exposure of enchytraeids to 10 mg/kg of tetrabromobisphenol A (TBBPA) resulted in significant effects on reproduction while decabromodiphenyl ether (DeBDE) was not shown toxic effects; on the other hand, TBBPA and hexabromocyclododecane diastereomers (HBCD a-, b- and c-) were absorbed by cabbage and radish plants in a short-term experiment (8 weeks), the soil matrix sorption resulted in a 90% decrease in the recovery of these compounds in the experimental soil, increasing the risk of exposure of plants by absorbing these compounds and improving their bioavailability; the results also provide information on the transport mechanisms of the TBBPA and HBCD diastereomers in the soilplant systems, showing a predominance of a-HBCD in bud tissues for both species which could be attributed to the specific translocation of HBCD diastereomer, change in the pattern of diastereomer and/or selective metabolism of c-HBCD within plants; soil nitrifying bacteria were only affected by short chain chloroparaffins (CP10-13) at EC10 concentration ¼ 570 mg/kg [42,45]. Navarro et al. [45a] determined the bioaccumulation behaviour of halogenated flame retardants (HFR) in three horticultural crops [two species, spinach (Spinacia oleracea) and tomato (Solanum lycopersicum L.) and corn (Zea mays)] and earthworms (Eisenia andrei), halogenated flame retardants were found in all soil samples treated with 5 mg of DeBDE/kg of soil. Transfer factors (TF), which are important for the evaluation of compound-specific uptake by plants, were also determined in all crop plants with results ranging from 2 to 9 times in spinach, 2 to 34 times in tomato and 11 to 309 times in corn, indicating an efficient uptake behaviour; bioaccumulation factor (BAF) values in earthworms were also higher for PFAS (4.06  2.23) than PBDE (0.02  0.02) [46]. Based on the data generated, a PNEC for soil organisms can be estimated at 0.3 mg/kg for TBBPA and 57 mg/kg for short chain chloroparaffins [42]. The toxic effects of halogenated flame retardants on terrestrial soil organisms have also been reported. A bioaccumulation behaviour study of 29 HFR in soil vertebrates (Eisenia andrei) showed an increase in concentrations of 1.1 to 2.4 times for polybrominated diphenyl ethers (PBDE) and 1.1 to 3.6 times for chlorinated flame retardants (CFR); bioaccumulation factors (BAF) were calculated to assess the degree of exposure of pollutants in earthworms, reporting average BAF values of 0.6–17 for PBDE and

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0.5–20 for CFR, which had an effect on ageing (21 days) and on the bioavailability of contaminants in modified soils [47]. Studies by Rothenbacher and Pecquet do not show any significant effect of TBBPA on soil nitrogen transformation, up to the highest concentration 1000 mg/kg (d.w.); on the other hand, the mortality for earthworms for 28 days was greater than 4840 mg/kg d.w., and the most sensitive terrestrial endpoint was the reproduction of earthworms with a maximum average effective concentration (EC50) of 0.12 mg/kg d.w. soil [48]. The use of the bioindicator Eisenia fetida has been a useful tool in assessing the toxic effects of the organic flame retardant Dechlorane Plus (DP). Studies by Yang and collaborators showed the effects on oxidative stress, enzymatic activity (neurotoxicity and cellulose) and DNA damage by exposure of earthworm to DP (0.1–0.5 mg/kg) for 28 days, ruling out effects on the mortality and weight, concluding that long-term exposure is a cause of stress in the bioindicator, and that oxidative stress plays an important role in toxicity. Exposure to concentrations of 0.1, 0.5, 6.25 and 12.5 mg/kg of PD showed no significant effects on body weight or lethality, but caused an increase in the markers of oxidative stress malonaldehyde (MDA) and 8-hydroxy-20 -deoxyguanosine (8-OHdG), and altered activities of acetylcholinesterase (AChE) [49,50]. Exposure of Eisenia fetida with polychlorinated biphenyls (PCBs)enriched soils caused significant weight loss in worms and an increased activity of catalase (CAT) and superoxide dismutase (SOD) in exposed earthworms for 7 or 14 days; in addition, PCB exposure triggered dosedependent coelomocyte (gut cells) DNA damage. The SOD and CAT activity increased significantly after 21 and 28 days of exposure of Eisenia fetis to decabromodiphenyl ether (BDE-209; 1, 10 and 100 mg/kg), while peroxidase (POD) and glutathione-s-transferase (GST) activity decreased, indicating a tendency of opposite response hydroxyl radicals (OH) were significantly induced by BDE-209 in earthworms and changes in malondialdehyde (MDA) content suggested that reactive oxygen species (ROS) could lead to cellular lipid peroxidation, indicating the production of severe oxidative stress in E. fetida [51]. Shi and colleagues determined the molecular mechanism of antioxidant defence through growth inhibition and transcription levels of antioxidant enzyme genes (SOD, CAT and the stress response gene involved in oxidative stress prevention (hsp70)) of earthworms (Eisenia fetida) exposed to TBBPA, HBCD and BDE-209, which represent the highest volume of

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brominated flame retardants. The results showed a significant positive regulation of SOD expression level in exposed earthworms at 50 mg/kg d.w. of TBBPA (1.77 times) and 400 mg/kg d.w. of HBCD (2.06 times); the same behaviour was observed with the transcription level of the hsp70 gene, increasing 2.16–2.19 times with TBBPA and 2.61 times with HBCD and no significant variation in the expression of the cat gene in all treatments with BFR, nor the level of expression of the target gene exposed to BDE-209 [52]. Using natural and artificial soils as substrate, Xie et al. examinated the effects of BDE-209 on avoidance response, survival, growth, and reproduction of E. fetida; the results showed that no significant avoidance response nor significant effects on survival and growth of adult earthworms was observed when were exposed to 0.1–1000 mg/kg of BDE-209 for 48 h, and no significant effects on reproductive parameters (e.g., cocoon production per earthworms, weight per cocoon and cocoon hatchability) were observed, suggesting that adult earthworms have a strong tolerance for BDE-209 exposure in soils, but a potential toxicity does exist for earthworm embryos or juveniles [53]. Sorge and Clark exposed earthworms (Lumbricus terrestris) to 50 and 250 ng/g dry soil of PBDE-99 for 1 week and the gut cells (coelomocytes) showed a significant increase in the percentage of cells exhibiting red cytosol per minute, indicating cellular damage due to the decreased lysosomal membrane stability, suggesting molecular mechanism in which PBDEs impaired cellular activity in the earthworm model, potentially making the cells susceptible to degradation by their own hydrolytic enzymes [54].

4. Ecotoxicity of HFR in water The flame retardant has been widely employed in recently years and the effects on the aquatic ecosystems still unclear. Several studies in the recent 10 years have been performed in diverse marine and freshwater organisms to clarify the toxicity effects and mechanisms. Table 2 shows the effects find in different marine organisms by exposure to FR. Table 3 shows the effects of FR on fresh water organisms. In both ecosystems are similar characteristics of toxicology, e.g., induce ROS, binds and modify hormone receptor and are accumulative in some tissues like liver and brain, and some of them drives in abnormal behaviour and neurodevelopmental and causes embryos and teratogenesis.

Table 2 Toxicity studies of HRF in different marine aquatic organisms. Exposure FR class Family Concentration time Organisms Effects

TBBPA

BDE-47

Mytilus Induce apoptosis, oxidative and immune stresses and disruption in [55] galloprovincialis energy, protein and lipid metabolisms in both male and female mussels with different mechanisms

18.4 nmol/L

1m

0.025, 0.25, 2.5 μg/L

6, 12, Tigriopus 24 h and japonicus 1, 4, 7 d

0.1, 1, 10 μg/L

2 hpf to 14 d

Paracyclopina nana

Transcription levels of DNL-related genes were increased upon [56] 2.5 μg/L 24 h. Palmitic acid was significantly increased at days 1 and 4 upon 2.5 μg/L. Docosahexaenoic acid and arachidonic acid were downregulated at days 1 and 4. Lipid droplet area increased in Nile red staining analysis upon 2.5 μg/L BDE-47 Induced oxidative stress (e.g., reactive oxygen species, ROS) mediated [57] activation of extracellular signal-regulated kinase (ERK) and c-Jun-Nterminal kinase (JNK) signalling cascades in MAPK pathways The stress stimulated the conversion of saturated fatty acids (SFAs) to polyunsaturated fatty acids (PUFAs), in consequence the development in embryos delays

0.89–0.94 and 1 m 9.50–9.80 μg/L

Mytilus Induced cell apoptosis and reduced reactive oxygen species (ROS) galloprovincialis production in both male and female mussels, disturbance in protein homeostasis

[58]

1, 10, 100 mg/Kg wet weight

Acipenser sinensis

[59]

14 d

Increase HP-70 stress protein and decrease small G-protein signal cascades Rab6B, Ca (2 +) signalling pathway annexin A4

Continued

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BDE-209

Br

Reference

Table 2 Toxicity studies of HRF in different marine aquatic organisms.—cont’d Exposure FR class Family Concentration time Organisms Effects

HBCD

Br

TDCIPP

Cl

Dechlorane Plus

TMCP a

OP

0, 100, 250 μg/L

50 d

Macoma balthica

Increase nuclear and nucleolar abnormalities and in the frequency of [60] dead cells was observed during the duration of the experiment with the highest peak occurring 10 days and 20–30 days after exposure the ribosomal genes (NORs) malfunction

1 or 10 a

40 d

Oncorhynchus tshawytscha

1 PBDE diet were more susceptible to L. anguillarum than salmon [61] fed, but surprisingly 10  PBDE were not more susceptible to the pathogen than salmon fed the control diet

20 and 0.50 μM

48h 20 d

Artemia franciscana

Acute: aspartate, phenylalanine, glycine, phosphocholine, betaine, taurine, gadusol, glycerol and trehalose levels increased, while methanol, methionine, and leucine levels decreased Chronic: glucose, phosphocholine, betaine, taurine, and gadusol increased, whereas tyrosine, serine, threonine, aspartate, glutamate, phenylalanine, glycerol, trehalose, and glycerophosphocholine decreased

0.001, 0.01, 0.1 and 1.0 μg/L

29 d

Mytilus edulis

Accumulated DP in muscle and digestive gland in a dose-dependent [63] manner. LPO levels in gills increase 82% and 67% at the 0.01 and 1.0 μg DP/L, respectively

Mejillo´n

COX activity in gills decreased by 44% at the 1 μg/L dose

Sparus aurata hepatocytes

Increased hepatocellular lipid content (cholesterol, triglyceride) by miRNAs

0.1, 1, 10 μM 48 h

[62]

[64]

Concentration finding in stomach contents of fish on the lower Willamette River near Portland. TBBPA, tetrabromobisphenol A; TMCP, tri-m-cresyl phosphate; BDE-47, tetrabromodiphenyl ether; BDE-209, decabromodiphenyl ether; TDCIPP, tris(1,3-dichloro-2-propyl) phosphate; HBCD, hexabromocyclododecanes; BDE-99, 2,20 ,4,40 ,5-penta-bromodiphenyl ether; BDE-100, 2,20 ,4,40 ,6-penta-bromodiphenyl ether; BDE-153, 2,20 ,4,40 ,5,50 -hexa-bromodiphenyl ether; BDE-154, 2,20 ,4,40 ,5,60 -hexa-bromodiphenyl ether; h, hours; d, days; m, months.

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Mix of BDE-47, BDE-99, BDE100, BDE-153 and BDE-154

Reference

Table 3 Toxicity studies of HRF in fresh water organisms. Exposure FR class Family Concentration time

Organisms

Effects

Reference

96 h

Danio rerio

Both TBBPA and BDE-47 caused tissue-specific [65] changes in thyroid receptor and deiodinase enzyme expression, with the brain, liver, pronephric ducts and craniofacial tissues appearing particularly responsive to altered TH signalling

TBBPA

5 μM

8–48 hpf

Danio rerio

TBBPA-induced apoptotic cell death, delayed [66] cranial motor neuron development, inhibited primary motor neuron development and loosed muscle fibre during the early developmental stages. To further explore TBBPA-induced developmental and neurobehavioural toxicity, RNA-Seq analysis was used to identify early transcriptional changes following TBBPA exposure

BDE-47

0.06, 0.2, 0.6 μM

72 hpf

Danio rerio

Produce vascular toxicity, decreases expression in [67] genes related with remodelling and vascular growth, the growth of common cardinal vein and the ventral diameter diminishes

1.25, 5, 20 μM

6–72 hpf

Danio rerio

Decrease spontaneous movement, touch response [68] and free-swimming speed Altered larvae swimming behaviour in response to light stimulation in developing zebrafish. Inhibited axonal growth of primary and secondary motor neurons during the early developmental stages

10, 100, 1000 ng/g

21 to 90 dph

Danio rerio

Decrease swimming distance and percent active, [69] without affecting body size or gonadal development

Br

Continued

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1–100 μM

BDE-47 and TBBPA

Table 3 Toxicity studies of HRF in fresh water organisms.—cont’d Exposure FR class Family Concentration time

PBDE-47, PBDE-99, PBDE-153

BDE-209

Cl

Effects

Reference

0.1 μM

6 hpf to 5 dph

Danio rerio

In zebrafish developmentally exposed to PBDE-47 [70] exhibited a worsening performance upon retest suggesting poorer memory retention or altered motoric effects

0, 3, 30 or 300 μg/L

28 d

Danio rerio

Abnormalities in offspring and a significant decrease [71] in T4 concentrations in F1 larvae 120 hpf. trα, trh, tshβ and dio1 were significantly downregulated in F1 individuals, while expressions of tshr and ttr were significantly upregulated

50–1000 ng/g 21 d weight

Oncorhynchus TT4, the concentration levels increased. With regard [72] mykiss to FT3, the concentrations in all treatment groups were significantly decreased especially for the dose of 100 ng/g. For FT4, the concentration level first decreased and then increased with dose. When the exposure dose was of 50 and 1000 ng/g, the FT4 concentration was not significantly changed. While at the dose of 100, 200, 500 ng/g, the FT4 concentration decreased significantly

1–100 μM

96 h

Danio rerio

5, 50, 500 μg/L

2–120 hpf

Induces autophagy

1/100–1/20 (LC50)

96 h

Induces oxidative stress, cell cycle arrest, DNA [75] damage and apoptosis in adult zebrafish liver in sexand concentration-dependent manners

Induce thyroid disruption and inhibition of growth [73] in offspring, and that perturbation of the HPT axis and GH/IGF axis contribute to these adverse effects [74]

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TDCIPP

Br

Organisms

100, 300, 600, From 2 to 900 μg/L 120 hpf

Cl

0, 4, 20 and 100 μg/L

2 hpf to 21 d

0, 4, 20, 100 μg/L

2 hpf to 6 m

Danio rerio

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TDCIPP

Decreased expression of the neuron-specific GFP in [76] transgenic zebrafish larvae as well as the expression of the neural marker genes elavl3 and ngn1. Also inhibited the axonal growth of the secondary motoneurons and altered the expressions of axonrelated genes in zebrafish larvae. At 900 μg/L significantly increased the activity of acetylcholinesterase, and decreased the total acetylcholine Increased plasma estradiol and testosterone levels in females, but had no effect in males and decreased egg production. Hepatic vitellogenin (vtg1 and vtg3) expression was upregulated in both females and males. Promotion of oocyte maturation in the females, but retardation of spermiation in males. Reduced egg quality and increased malformation rates in the F1 generation. TDCIPP and its metabolite bis(1,3-dichloro-2-propyl) phosphate were found in the gonads [77] Concentrations of TDCIPP and its metabolic product (bis(1,3-dichloro-2-propyl) phosphate) were measured in the tissues of 5 dph larvae. However, in adult fish, reductions of dopamine and serotonin levels were detected in the brains of females but not males. Downregulation of nervous system development genes in brain tissues of both male and female. TDCPP concentrations were measured in female’s adult fish tissues, in brain, and greater levels were detected Continued

Table 3 Toxicity studies of HRF in fresh water organisms.—cont’d Exposure FR class Family Concentration time

TBOEP

OP

21 d

0.02, 0.1 or 0.5 μM

120 hpf

2–5000 μg/L 3–120 hpf

Effects

Reference

17β-Estradiol increased in both sexes of fish and [78] testosterone only in male fish. Transcription of genes along the HPG axis increased in both male and female fish. Decreases the average number of eggs production, as well as hatching success and survival rates in offspring. Histological examination shows inhibition of oocyte maturation in females and retardation spermiation in males. TBOEP disturb the sex hormone balance by altering regulatory circuits of the HPG axis; affect gonadal development, eventually leading to disruption of reproductive performance and the development of progeny Danio rerio

At 0.5 μM upregulated expression of oestrogen [79] receptors indicates that TBOEP module the ER pathway. Mineralocorticoid receptor pathway was significantly downregulated. In mammalian cells, none of these pathways were affected by TBOEP at the concentrations studied

Danio rerio

TBOEP causes lethality, reduced growth, [80] malformations, and edema, in early life stages of zebrafish in a time- and concentration-dependent manner. Relatively small, environmentally relevant concentrations of TBOEP (2 μg/L) induced expression of several genes, whereas higher concentrations of 20 or 200 μg/L generally reduced transcription of other genes, mostly involved in steroidogenesis

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0, 5, 50, 500 μg/L

Organisms

TBP

Danio rerio

0, 0.2, 0.4, 0.8, 1.2 and 1.6 mg/L

72 h

Phaeodactylum Inhibited growth of the parasite P. tricornutum in a clear [82] tricornutum dose-response manner. Algal cells treated with TBP exhibited distorted shapes, ruptured cell membranes and damaged organelles, especially mitochondria lead to apoptosis. Although the activities of two antioxidant enzymes, superoxide peroxidase and catalase, were upregulated, excess ROS and malondialdehyde accumulated in algal cells after exposure

1% DL50

0.6 d

Danio rerio

Induces smaller posterior swim bladder and increased [83] expression in the gene encoding thyroid peroxidase, tpo and the genes encoding two swim bladder surfactant proteins, sp-a and sp-c

Daphnia magna Limnodrilus hoffmeisteri Carassius auratus livers

TBBPA was more toxic to D. magna and L. hoffmeisteri [84] in acidic conditions. The effect is synergic between DMSO and TBBPA. The oxidative stress study showed that the activity of SOD, CAT, and GST and the GSH levels in all treated groups were altered by TBBPA exposure, which indicates that TBBPA enhanced the production of ROS and induced the oxidative stress in C. auratus, low pH and DMSO enhanced its toxicity

0–28 dph TBBPA

3.58 mM

24 h

Continued

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PFOA, TBBPA, TDCPP, DOPO and PFBA

OP

At 150 or 800 μg/L TBEP inhibited the degradation [81] and utilization of vitellogenin and downregulated the expression of proteins related to cation binding, lipid transport, uptake and metabolism, accompanied by a decrease in heart rate and body length. Decreased the expression of proteins involved in cell proliferation and DNA repair, and led to an increased number of apoptotic cells in the tail region

0, 0.8, 4, 20 or 4–120 hpf 100 mg/L 0, 150 or 800 μg/L

Table 3 Toxicity studies of HRF in fresh water organisms.—cont’d Exposure FR class Family Concentration time

0.35, 0.50, 0.71, 1.01, 1.43, 2.00 mg/L

BTBPE EH-TBB

Br

Br

Effects

Carassius auratus

Higher than 0.71 mg/L for an exposure period of [85] 32 days, GST, AST, ALT, and UDPGT activities cannot be restored to normal levels, suggesting irreversible damage. The activities of AST, ALT, and GR increased more significantly than GST and UDPGT at the lowest concentration of 0.35 mg/L. AST and ALT are suitable for use in conventional monitoring of water quality in areas at risk for TBBPA pollution

1, 10, 100 nM 24 to finish Frog: Induce gonadal masculinization methamorphosis Pelophylax nigromaculatus

Reference

[86]

1 and 10 μM 1–144 hpf

Danio rerio

51.5 μg/g 5.5 μg/g

Juvenile At 28-day, bioaccumulation: 76%, BTBPE and 2%, [88] Onchorynchus EH-TBB. BTBPE impacted the transcription of mykiss 33 genes, including genes involved in the immune response, reproduction, and oxidative stress

48 h, 28 d

TBECH delays hatching at 1 and 10 μM doses while [87] morphological abnormalities and juvenile mortality was observed at 10 μM. Also alter of multiple genes involved in chondrogenesis (cartilage development), metabolism and stress response

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TBECH

32 d

Organisms

HBCD

Br

80, 300 and 800 mg/L 0, 8, 30, 80, 300 and 800 mg/L

96 h

Oryzias melastigma

Induced malformation, increase of heart rate and [90] changes of the heart structures in embryo in development, and induced the expression of TNFα and IL-1β, which then stimulated the formation of ROS. The excessive amount of ROS leads formation of DNA oxidative damages

10 mg/Kg food

21 d

Oncorhynchus The accumulation begins after 6 h, with a peak in [91] mykiss 6–8 days, after 21 days HBCD was eliminated in liver and brain but not in muscle

0, 0.05, 0.1, 0.5, and 1.0 mg/L

4–96 hpf

Danio rerio

TPHP 5, 25, 14 d 125, 625 μg/ L, TNBP and

Exposure to 0.1, 0.5, and 1.0 mg/L significantly [92] increased the malformation rate, but only the 0.5 and 1.0 reduced survival. Increase ROS and apoptotic genes like p53, Puma, Apaf-1, caspase-9, and caspase3, Mdm2 and Bcl-2 were downregulated activity of capspase-9 and caspase-3 was significantly increased

Oryzias latipes The OP testes decrease hatchability, delay time to [93] hatching, increase the occurrence of malformations, reduce body length, and slow heart rate Continued

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Induced the transcription of oxidative stress response [89] genes and apoptotic genes, e.g., SOD, CAT, GST, OGG1, P53 and Caspase-3. Induced the generation of reactive oxygen species in T. japonicus, which activated the oxidative stress defence genes and meanwhile resulted in oxidative DNA damage. The damaged DNA activated the transcription of p53 and triggered the caspase-mediated apoptosis pathway, which may be the reason for the tHBCD induced developmental delay in T. japonicus nauplii. The bioaccumulation was observed by multiple-generation

2 generation full-cycle

0, 5, 20 50 μM/L

Triphenyl phosphate, tri- OP n-butyl phosphate, tris(2butoxyethyl) phosphate,

Tigriopus japonicus

Table 3 Toxicity studies of HRF in fresh water organisms.—cont’d Exposure FR class Family Concentration time

Organisms

Effects

Reference

tris(2-chloroethyl) phosphate

3125 μg/L, TBOE and TCEP P 50, 250, 1250, and 6250 μg/L

Halogenated and organophosphate compounds

6.4 nM to 64 μM

6–120 hpf

Danio rerio

The OP and halogenated flame retardant induce diverse abnormalities in neurodevelopment

TPhP TCEP

0.10, 0.50, 1.0 mg/L TPhP 0.10, 0.50, 1.0 mg/L CDP

2–96 hpf

Danio rerio

The aryl-OPFRs have greater heart developmental [95] toxicity than alkyl-OPFRs. Acute toxicity of OPFRs varied mainly depending on their hydrophobicity. The specific cardiac developmental defects caused by TPhP and CDP might be related to the disturbed expressions of transcriptional regulators, especially the downregulations of BMP4, NKX2–5 and TBX5. Arrhythmia and cardiac looping defects can be easily induced at 0–24 hpf and 12–48 hpf, respectively, under TPhP and CDP exposure in zebrafish embryos

TPhP, TTP

0, 1, 10, or 100 μg/L 0, 1, 3, or 10 mg/L

48 h

Rat pituitary (GH3) and thyroid follicular (FRTL-5)

In GH3 cells, TPhP upregulated the expression of the [96] tshβ, trα, and trβ genes. In the FRTL-5 cells, the expression of the nis and tpo genes was significantly upregulated, suggesting that TPP stimulates thyroid hormone synthesis in the thyroid gland

Changes of acetylcholinesterase activity and transcriptional responses of genes related to the nervous system likely provide a reasonable explanation for the neurobehavioural disruption

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24 h

[94]

0, 40, 200, 500 μg/L

cell lines Danio rerio

7 days post-fertilization, TPhP exposure leads to significant increases in both T3 and T4 concentrations and expression of the genes involved in thyroid hormone synthesis. Exposure also significantly upregulated the expression of the genes related to the metabolism (dio1), transport (ttr), and elimination (ugt1ab) of thyroid hormones. The downregulation of the crh and tshβ genes

0, 5, 50, 500 μg/L

21 d

Daphnia magna

Body lengths decreased of both F0 and F1 generation [97] and inhibited the fecundity of F0 generation. RT-qPCR showed that the expressions of 76 genes involved in 15 pathways were significantly altered after exposure to 500 μg/L TPHP for 21 days. The significantly increase pathways related to genetic information processing, cellular process and metabolism

0.05, 50 μM

5–72 hpf

Danio rerio

TPP, increase fivefold and posterior decrease in cyp26a1 expression, a major target gene for RA-induced RAR activation

0, 0.8, 4, 10, 4–72 hpf 500 mg/L

Danio rerio

Both of them induce smaller rates of hatching and [99] survival, in dose- and time-dependent manners. The expression of mRNAs involved in aryl hydrocarbon receptors, peroxisome proliferator-activated receptor alpha, estrogenic receptors, thyroid hormone receptor alpha, glucocorticoid receptor, and mineralocorticoid receptor centred gene networks was altered

[98]

Continued

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TDCPP and TPhP

7 dph

Table 3 Toxicity studies of HRF in fresh water organisms.—cont’d Exposure FR class Family Concentration time

Organisms

Effects

Reference

Br

607 or 58 μg/g food

Oryzias latipes Cumulative fecundity was 18% lesser to 58 μg TBCO/ [100] g, wet mass food. However, fecundity tested at 607 μg TBCO/g, wet mass food has not change. Organspecific and dose-dependent alterations to abundances of transcripts were observed in male and female fish. A pattern of downregulation of expression of genes involved in steroidogenesis, metabolism of cholesterol, and regulatory feedback mechanisms was observed in gonads from male and female fish which had been exposed to the greater concentration of TBCO. However, these effects on expression of genes were not manifested in effects on fertilization of eggs or fecundity. In livers from male and female fishes exposed to the lesser concentration of TBCO, greater expression of genes that respond to exposure to estrogens, including vitellogenin II, choriogenin H, and ER were observed

TBPH and TBB

Br

1500 or 150 μg/g food

Oryzias latipes A sex-specific downregulation of gene transcription at [101] all levels of the HPGL-axis; in female fish, the abundance of transcripts of ERα was lesser in livers, while abundances of transcripts of VTG II and CHG H were greater. In male medaka, abundances of transcripts of ERα, ERβ, and ARα were lesser in gonads and abundances of transcripts of ERβ and ARα were lesser in brain. Abundances of transcripts of genes encoding proteins for synthesis of cholesterol, transport of cholesterol, and sex hormone steroidogenesis (CYP 17 and 3β-HSD) were significantly lesser in male medaka, which might have implications for concentrations of sex hormones

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TBCO

OPh

0.1–1.6 μM

6–120 hpf

Danio rerio

mITP causes AHR-independent cardiotoxicity through a pathway that is also antagonized by CH223191

[102]

PBDE-47 PBDE-99 PBDE-153

Br

0.1 μM

6 h to 5 d

Danio rerio

Zebrafish developmentally exposed to PBDE-47 exhibited a worsening performance upon retest suggesting poorer memory retention or altered motoric effects

[70]

6-OH-BDE-47

Br

10–100 nM

4–30 hpf

Danio rerio

100 nM concentration resulted in a 26% decrease in [103] head trunk angle, a 54% increase in otic vesicle length, and a 42% decrease in eye pigmentation. These effects may be resulting from altered thyroid hormone regulation in vivo through downregulation of the thyroid hormone receptor

BDE-209, TBBPA, HBCD, DBDPE, HBB and PBT

10 and 100 μg/kg

7, 14, 30 d

Carassius auratus

Oxidative stress was evoked evidently for the [104] prolonged exposure, represented by the significantly altered indices (superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, and malondialdehyde). The integrated biomarker response (IBR) index ranked biotoxicity as: PBT > HBB > HBCD > TBBPA > BDE209 > DBDPE

TBBPA and HBCD

TBBPA, 2 hpf to 96 h 0.002, 0.01, 0.05, 0.25, 0.75, 1.5 mg/L for HBCD, 0.002, 0.01, 0.5, 2.5, and 10 mg/L

Danio rerio

TBBPA and HBCD cause oxidative stress (increase [105] SOD, LPO) and Hsp70 overexpression, inducing acute toxicity to zebrafish embryo in a short-term exposure

Continued

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mITP

Table 3 Toxicity studies of HRF in fresh water organisms.—cont’d Exposure FR class Family Concentration time

Organisms

Effects

TDCPP and TPP

Danio rerio

Decrease in fecundity along with significant increases of [106] plasma 17β-estradiol concentrations, vitellogenin levels, and E2/testosterone and E2/11-ketotestosterone ratios were observed. The transcriptional profiles of several genes of the hypothalamus-pituitary-gonad axis changed as well after the exposure, but the trend was sex-dependent. In male fish, gonadotropin-releasing hormone2 (GnRH2), GnRHR3, cytochrome P450 19B, oestrogen receptor α, ER2β1, and follicle stimulating hormone β were upregulated in the brain, while luteinizing hormone β and androgen receptor 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

ClPO

0.04, 0.2, 1 mg/L

21 d

Reference

ARTICLE IN PRESS

Br

30 ng mixed

21 d

TCEP, TCPP, TDCPP, TBEP, TPP, and TCP

Cl and 0.001, 0.01, 48 h OP 0.1, 1, 10, or 100 mg/L TDCPP (0, 0.04, 0.2, 1 mg/L), TPP (0, 0.04, 0.2, 1 mg/L), TCP (0, 14 d 0.008, 0.04, 0.2 mg/L)

Snapping turtle, fathead minnow, Ciprinus carpio, mouse

Except for the snapping turtle’s inability to [107] metabolize EH-TBB, very similar metabolic rates between minnow, carp, and mouse were observed for both EH-TBB and TBPH. EH-TBB was consistently metabolized to a greater extent than TBPH across all species tested in this study. The similarity found in EH-TBB and TBPH metabolism between the fish and mouse suggests that enzymes responsible for this metabolism might be similar between the two species

[108] H295R, All six OPFRs increased both 17β-estradiol and MVLN cells testosterone concentrations in H295R cells. With MVLN, four major steroidogenic genes was upregulated and that of two sulfotransferase genes was downregulated. In MVLN cells, no OPFRs acted as oestrogen receptor agonists, while TDCPP, TPP, and TCP acted as antagonists inhibiting binding of E2 to oestrogen receptor Danio rerio After 14 d of zebrafish exposure, TCP, TDCPP, or TPP significantly increased plasma T and E2 concentrations, but did not change 11-ketotestosterone among female fish. Among males, both T and 11-KT decreased and E2 increased. In general, transcription of CYP17 and CYP19a genes was significantly upregulated in both sexes, while vitellogenin1 gene was down- and upregulated in female and male fish Continued

ARTICLE IN PRESS

EH-TBB TBPH

Table 3 Toxicity studies of HRF in fresh water organisms.—cont’d Exposure FR class Family Concentration time

1 μM for BDE-15 BDE-47; 5 μM for TBBPA

4h

Hexabromocyclododecane Br (HBCD) diastereoisomers

0.01, 0.1, 1.0 mg/L

4–120 hpf

Effects

Reference

Carassius auratus liver

The biotransformation of BDE-15 and TBBPA in [109] fish liver is mediated by cytochrome P450 enzymes, as revealed by the formation of hydroxylated metabolites and oxidative bond cleavage products. CYP1A was the major enzyme responsible for the biotransformation of BDE-15 and TBBPA in fish liver The diastereoisomers α-, β- and γ-HBCD at [110] 0.01 mg/L had little effect on the development of zebrafish embryos except that exposure to 0.01 mg/L γ-HBCD significantly delayed hatching. At 0.1 mg/L, α-HBCD resulted in depressed heart rate of larvae and delayed hatching, whereas β- and γ-HBCD both caused significant hatching delay and growth inhibition. In addition, a remarkable and significant increase in mortality and malformation rate was noted at 0.1 mg/L γ-HBCD exposure groups. At 1.0 mg/L, α-, β- and γ-HBCD significantly affected all of the endpoints monitored. Additionally, HBCD diastereoisomers could induce the generation of reactive oxygen species and the activities of caspase-3 and caspase-9 in a dosedependent manner

ARTICLE IN PRESS

BDE-15 BDE-47 TBBPA

Organisms

BDE-47 BPA TBBA

Br

Danio rerio Embryos Larva’s

In embryos, BDE-47 significantly induced the [111] sodium iodide symporter and thyroid stimulating hormone. TBBPA significantly induced thyroid receptor α and thyroid stimulating hormone, while BPA did not significantly induce any of the genes. Most genes were only induced at the 75% 96 h-LC50 or 96 h-EC50; however, thyroid peroxidase and thyroid stimulating hormone demonstrated upregulation in a level as little as the 10% 96 h-LC50 value. TBBPA > BPA > BDE-47 In larvae, BDE-47 was found to have significantly induced many genes of interest, namely, thyroglobulin, thyroid peroxidase, thyroid receptors α and β, thyroid stimulating hormone, and transthyretin. TBBPA only significantly induced three genes, thyroid receptor α, thyroid stimulating hormone, and transthyretin while BPA only induced thyroid stimulating hormone. The relative toxicity could express TBBPA > BDE-47 > BPA based on their 96 h-LC50

TBBPA (0.5, 3 h to 5 d 0.75, 1, 1.5, 3 μM) BPA (5, 10, 15, 20, 25 μM) DME (5, 10, 15, 20, 25 μM)

Danio rerio

TBBPA is more toxic than others. All three caused [112] edema and haemorrhage; only TBBPA specifically caused decreased heart rate, edema of the trunk, and tail malformations The expression of matrix metalloproteinase (MMP) MMP-2, -9 and -13 increased (two- to eightfold) after TBBPA exposure followed by an increase in the degradation of collagen I and gelatin Continued

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TBBPA, BPA and TBBPA Br DME

10%, 25%, 30 s–4 min 50%, 75% of 96 h LC50

Table 3 Toxicity studies of HRF in fresh water organisms.—cont’d Exposure FR class Family Concentration time

Br

0–250 μM

DE-71

Br

0, 1, 3, and 10 μg/L

4 hpf to 14 d

Effects

Reference

Cyprinus carpio liver

Cyprinus carpio hepatocytes metabolize BDE-99 via a [113] reductive pathway and that the enzymes catalysing this reaction are likely associated with the endoplasmic reticulum, but a minor part occurs in cytosolic fraction

Danio rerio

Transcription of corticotrophin-releasing hormone [114] and thyroid stimulating hormone beta, genes were upregulated and reduced thyroxine (T4) levels

Abbreviations: BDE-47, tetrabromodiphenyl ether; TBBPA, tetrabromobisphenol A; BDE-209, decabromodiphenyl ether; TDCIPP, tris(1,3-dichloro-2-propyl) phosphate; PFOA, perfluorooctanoic acid; TBBPA, tetrabromobisphenol A; DOPO, 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxdie; PFBA, perfluorobutyric acid; TBECH, tetrabromoethylcyclohexane; TBP, tributhylphosphate; BTBPE, 1,2-bis(2,4,6-tribromophenoxy) ethane; EH-TBB, 2-ethylhexyl-2,3,4,5-tetrabromobenzoate; HBCD, hexabromocyclododecanes; TPhP, triphenyl phosphate; TCEP, tris(2-chloroethyl) phosphate; TDCPP, tris(1,3-dichloro-2-propyl) phosphate; TBCO, 1,2,5,6-tetrabromocyclooctane; TBPH, bis(2-ethylhexyl)2,3,4,5-tetrabromophthalate; TBB, 2-ethylhexyl-2,3,4,5 tetrabromobenzoate; mITP, mono-substituted isopropylated; 6-OH-BDE-47, 6-hydroxy-2,20 ,4,40 -tetrabromodiphenyl ether; DBDPE, decabromodiphenyl ethane; HBB, hexabromobenzene; PBT, pentabromotoluene; TCEP, tris(2-chloroethyl) phosphate; TCPP, tris(2-chloroisopropyl) phosphate; TDCPP, tris(1,3-dichloro-2-propyl) phosphate; TBEP, tris(2-butoxyethyl) phosphate; TPP, triphenylphosphate; TCP, tricresylphosphate; DME, dimethyl ether. Hpf, hours post-fertilization; dph, days post-hatching; h, hours; d, days; m, months.

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BDE-99

Organisms

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29

5. Conclusions In conclusion, due to their physicochemical properties and ability to bioaccumulate HFRs are capable of producing various toxic effects, in this review we focus on the main ones found in organisms that inhabit the different matrices of the environment, such as birds (air), plants and earthworms (soil) and aquatic organisms (water), being the ones that are reported in the highest incidence are changes in behaviour, physical and neurological abnormalities, changes in reproduction, size and therefore damage to the population, so it is of the utmost importance continuing with the study of these chemical compounds and their possible impact on organisms and human should continue, in order to reduce or prohibit their use, as well as to generate techniques for their effective removal of the different matrices.

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