Anaerobic treatment removing tetrabromobisphenol A and biota safety: How do tropical aquatic species respond to effluent toxicity over short- and long-term exposures?

Wastewater containing tetrabromobisphenol A (TBBPA), a commonly used flame retardant found in wastewater, can present significant toxic effects on biota, yet its impact on tropical freshwater environments is not well understood. This study explores the effectiveness of two independent anaerobic treatment systems, the acidogenic reactor (AR) and the methanogenic reactor (MR), for the ecotoxicity reduction of TBBPA-rich wastewater in four tropical freshwater species. Despite presenting good physicochemical performance and reduced toxicity of the influent for most species, AR and MR treatments remain acute and chronic toxicity. Overall, MR exhibited greater efficacy in reducing influent toxicity compared with AR. TBBPA bioaccumulation was observed in Chironomus sancticaroli after short-term exposure to 100% MR effluent. Multigenerational exposures highlighted changes in the wing length of C. sancticaroli, showing decreases after influent and AR exposures and increases after MR exposures. These findings underscore the need for ecotoxicological tools in studies of new treatment technologies, combining the removal of emerging contaminants with safeguarding aquatic biota. PRACTITIONER POINTS: Acidogenic and methanogenic reactors reduced the acute and chronic toxicity of wastewater containing tetrabromobisphenol A. Both treatments still exhibit toxicity, inducing short- and long-term toxic effects on four native tropical species. The aquatic species Pristina longiseta was most sensitive to effluents from acidogenic and methanogenic reactors. TBBPA concentrations recovered from Chironomus sancticaroli bioaccumulation analysis ranged from 1.07 to 1.35 µg g-1. Evaluating new treatment technologies with multiple species bioassays is essential for a comprehensive effluent toxicity assessment and ensuring aquatic safety.

Comparative effects of oral exposure to 2, 4, 6-tribromophenol and decabromodiphenyl ether in Nile tilapia.

Flame retardants are compounds added to a high diversity of polymers used in electronics and furniture to decrease the risk of combustion. Decabromodiphenyl ether (BDE-209) is a polybrominated diphenyl ether (PBDE) congener still used worldwide, while 2, 4, 6-tribromophenol(TBP) is a PBDE metabolite used as a pesticide and flame retardant for wood conservation. These compounds have lipophilic properties and are easily bioaccumulated in the food chain. In the current study, the acute and chronic toxicity of BDE-209 and TBP was evaluated in Oreochromis niloticus through analyses of redox imbalance, neurotoxicity, and histopathological biomarkers after acute (24, 48, 72, and 96 h) and chronic (90 days) exposure to 0.5, 5, and 50 ng/g of the polybrominated compounds. The results showed effects on glutathione S-transferase(GST) activity and damage to biomolecules in both acute and chronic exposures. Liver histopathology and the ultrastructure of hepatocytes revealed alterations and damage in individuals from both experiments, but only BDE-209 led to neurotoxic effects. The current study revealed new endpoints related to polybrominated compounds in fish, highlighting the need to review the risk of exposure to biota.

A comparison of developmental toxicity of brominated and halogen-free flame retardant on zebrafish.

Brominated diphenyl ethers (BDEs) are halogenated flame retardants. Several concerns related to persistence and toxicity of BDEs have been resulted in a growing need of BDEs replacement. The use of halogen-free flame retardants (HFFR) has increased as a safer alternative, but little information is available on their toxic potential for environmental health and for developing organisms. Therefore, the aim of this study was to evaluate and compare the toxicity of three congeners of BDEs (BDE-47, BDE-99 and BDE-154) with an HFFR (aluminum diethylphosphinate, ALPI) on zebrafish (Danio rerio) by assessing endpoints of lethality, sub-lethality and teratogenicity at the earlier stages of development. The highest tested concentration of BDE-47 (12.1 mg/L) induced pericardium and yolk sac edemas that first appeared at 48 h post-fertilization (hpf) and then were mostly reabsorbed until 144 hpf. BDE-47 also showed a slight but non-significant tendency to affect swim bladder inflation. The rate of edemas increased in a concentration-dependent manner after exposure to BDE-99, but there were no significant differences. In addition, the congener BDE-99 also presented a slight and non-significant effect on swim bladder inflation, but only at the highest concentration tested. Regarding BDE-154 exposure, the rate of edemas and swim bladder inflation were not affected. Finally, in all ALPI exposure concentrations (0.003 up to 30 mg/L), no sub-lethal or teratogenic effects were observed on developing organisms until 96 hpf. Although further studies are needed, our results demonstrate that when comparing the developmental toxicity induced by flame retardants in zebrafish, the HFFR ALPI may be considered a more suitable alternative to BDE-47.

Tris(2-chloroethyl) phosphate, a pervasive flame retardant: critical perspective on its emissions into the environment and human toxicity.

Regulations and the voluntary activities of manufacturers have led to a market shift in the use of flame retardants (FRs). Accordingly, organophosphate ester flame retardants (OPFRs) have emerged as a replacement for polybrominated diphenyl ethers (PBDEs). One of the widely used OPFRs is tris(2-chloroethyl) phosphate (TCEP), the considerable usage of which has reached 1.0 Mt globally. High concentrations of TCEP in indoor dust (∼2.0 × 105 ng g-1), its detection in nearly all foodstuffs (max. concentration of ∼30-300 ng g-1 or ng L-1), human body burden, and toxicological properties as revealed by meta-analysis make TCEP hard to distinguish from traditional FRs, and this situation requires researchers to rethink whether or not TCEP is an appropriate choice as a new FR. However, there are many unresolved issues, which may impede global health agencies in framing stringent regulations and manufacturers considering the meticulous use of TCEP. Therefore, the aim of the present review is to highlight the factors that influence TCEP emissions from its sources, its bioaccessibility, threat of trophic transfer, and toxicogenomics in order to provide better insight into its emergence as an FR. Finally, remediation strategies for dealing with TCEP emissions, and future research directions are addressed.

Exposure to decabromodiphenyl ether (BDE-209) produces mitochondrial dysfunction in rat liver and cell death.

Polybrominated diphenyl ethers (PBDE) are ubiquitous environmental pollutants. Exposure to these chemicals has been associated with developmental neurotoxicity, endocrine dysfunctions, reproductive disorders, and hepatotoxicity. The widespread use of PBDE as flame retardants has culminated in daily exposure of humans and wildlife to these contaminants and resulted in their banned use. Thus assessment of the potential effects of each PBDE congener on living organisms has become cause for concern. The aim of this study was to (1) examine the effects of decabromodiphenyl ether (BDE)-209 on different functions of HepG2 cells and (2) investigate whether this congener is involved in mitochondrial toxicity. The use of multiple methods was employed to (i) study the influence of BDE-209 on mitochondrial permeability transition (MPT) process in mitochondria isolated from rat liver and (ii) determine the consequential cellular damage. Our results showed that BDE-209 induced matrix swelling related to MPT with 10 µM and ATP depletion with 0.1 µM. In addition, 0.5 µM BDE-209 reduced HepG2 cell viability, produced collapse of membrane potential, but increased levels of reactive oxygen species (ROS) after 48 h incubation. After 24 h with 5 µM treatment elevated levels of ROS, DNA fragmentation and cytochrome c release, accompanied by caspase 9 and caspase 3 activation was noted. Taken together, these results suggest that short-duration exposure (24 or 48 h) to 0.5 µM or 5 µM BDE-209 concentrations diminished HepG2 cell viability due to apoptosis associated with mitochondrial dysfunction.

The effects of fluoride based fire-fighting foams on soil microbiota activity and plant growth during natural attenuation of perfluorinated compounds.

The use of fluoride based foams increases the effectiveness of fire-fighting operations, but they are also accompanied by major drawbacks regarding environmental safety of perfluorinated compounds (PFCs). The main concern with PFCs release is due to their well-known persistence and bioaccumulative potential, as they have been detected in many environmental samples. There is a significant knowledge gap on PFC toxicity to plants, even though such data could be useful towards bioremediation procedures. It is consensus that a realistic assessment of fire-fighting foam toxicity should cover as many test organisms as possible, however, few studies combine the performance of ecotoxicological tests with a detailed study of microbial communities in soil contaminated with firefighting foams. Our research evaluated the effects of natural attenuation of PFCs on the development of arugula and lettuce seeds. The effects of variable PFCs amounts were also observed in soil microbiota using the 2,6 dichlorophenol-indophenol redox dye as microbial metabolism indicator. We aimed to determine whether aqueous film forming foams toxicity increased or decreased over time in a simulated contamination scenario. We argued that the long-term biotransformation of fire-fighting foams should be taken in to account when evaluating toxicity, focusing on a time-based monitoring analysis, since potentially toxic intermediates may be formed though biodegradation. The phyto-toxicity of PFCs to lettuce and arugula was high, increasing as a function of the concentration and decreasing as a function of exposure time to the environment. However, very specific concentrations throughout biodegradation result in the formation of non-inhibiting intermediates. Therefore, variable biodegradation-dependent germination rates may be misleading on non-time-based monitoring approaches. Also, the low phyto-toxicity after 240days does not exclude the potential for PFC bioaccumulation in plants. We also proposed that the colorimetric data modelling could also establish a novel toxicity parameter to evaluate the release impacts to soil and biota. The combined assays allowed the monitoring of PFCs during long-term exposition to plants as well as their immediate effects on the same soil microbiota.

Association of prenatal and childhood PBDE exposure with timing of puberty in boys and girls.

BACKGROUND: Polybrominated diphenyl ether (PBDE) flame retardants are endocrine-disrupting chemicals that exhibit estrogenic and androgenic properties and may affect pubertal timing. METHODS: Study subjects were participants between 1999 and 2013 in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal cohort study of predominantly Mexican origin families in Northern California. We measured serum concentrations of four PBDEs (BDE-47, -99, -100, -153) in blood collected from mothers during pregnancy (N=263) and their children at age 9years (N=522). We determined timing of pubertal onset in 309 boys and 314 girls using clinical Tanner staging every 9months between 9 and 13years of age, and timing of menarche by self-report. We used Poisson regression for relative risk (RR) of earlier puberty and parametric survival analysis for time ratios (TR) of pubertal milestones. RESULTS: Prenatal concentrations of all 4 congeners and Æ©PBDEs were associated with later menarche in girls (RRearlier menarche=0.5, 95% confidence interval (CI): 0.3, 0.9 for Æ©PBDEs) but earlier pubic hair development in boys (RRearlier pubarche=2.0, 95% CI: 1.3, 3.3 for Æ©PBDEs). No associations were seen between prenatal exposure and girls' breast or pubic hair development or boys' genital development. Childhood PBDE exposure was not associated with any measure of pubertal timing, except for an association of BDE-153 with later menarche. CONCLUSIONS: We found that prenatal PBDE exposure was associated with later menarche in girls but earlier pubarche in boys, suggesting opposite pubertal effects in girls and boys.

Thyroid hormone disruption and cognitive impairment in rats exposed to PBDE during postnatal development.

Polybrominated diphenyl ether flame-retardants (PBDEs) are thyroid-disrupting environmental chemicals. We investigated the effects of postnatal exposure to DE-71 (a mixture of tetra- and penta-brominated congeners), n-propylthiouracil (PTU) and thyroxine (T4) replacement on open-field (OF) and radial maze (RAM) tests. Wistar rats (5 males/5 females per litter, 32 litters) were treated orally (PND 5-22) with PTU (4mg/kg bw/d), DE-71 (30mg/kg bw/d), with and without co-administration of T4 (15µg/kg bw/d, sc). PTU depressed T4 serum levels and body weight gain and enlarged thyroid gland. Although decreasing T4 levels, DE-71 did not change thyroid and body weights. PTU-treated rats showed hyperactivity (PND 42 and 70), and working and reference memory learning deficits (RAM, PND 100). Although not altering motor activity and working memory, DE-71 caused a reference memory deficit (females only). T4 co-administration averted hypothyroxinemia and long-term cognitive deficits caused by PTU and DE-71.

Evaluation of Polybrominated Diphenyl Ether Toxicity on HepG2 Cells - Hexabrominated Congener (BDE-154) Is Less Toxic than Tetrabrominated Congener (BDE-47).

Apoptotic cell death is one of the main consequences of exposure to brominated flame retardants, including polybrominated diphenyl ethers. However, few of these compounds have had their potential toxicity investigated. BDE-154 is one of the most poorly studied polybrominated diphenyl ether (PBDE) congeners, but its level in the environment and in biological fluids is rising. In addition, its chemical structure differs from the other congeners with well-documented toxicity, so BDE-154 may display a distinct toxicity pattern. This study has evaluated how BDE-154 affects the human hepatoblastoma cell line (HepG2) and has looked into the impact of this congener on human health. In addition, this study has related the effects of BDE-154 with the effects of BDE-47 to clarify the mechanism of PBDE toxicity. The HepG2 cell line was exposed to BDEs for 24 and 48 hr and submitted to assays to examine proliferation, viability, mitochondrial membrane potential, reactive oxygen species accumulation, phosphatidylserine exposure, nuclear fragmentation and evaluation of pro-caspase 3, pro-caspase 9, cytochrome c release, and apoptosis inductor factor release by Western blot analysis. BDE-154 induced mitochondrial damage and led to apoptotic death of HepG2 cells, but these effects were less intense than the effects promoted by BDE-47. Unlike other extensively reported congeners, BDE-154 was only toxic at the higher tested concentrations, whereas BDE-47 cytotoxicity was evident even at lower concentrations. Hence, like the toxicity pattern of other classes of substances such as polychlorinated biphenyls, the toxicity pattern of BDEs also depends on their chemical structure and aromatic substituent.

Comparative Study of Genotoxicity Induced by Six Different PBDEs.

Indiscriminate use of synthetic substances has led to environmental contamination and increasing human and animal exposure to harmful chemicals. Polybrominated flame retardants (PBDEs), which serve as non-covalent additives that enhance the safety of a variety of commercial and consumer goods, are an important class among potentially damaging synthetic substances. Its use is very common in developing countries, including Brazil. In theory, 209 different PBDE congeners exist, and many are currently being used during the manufacture of several products. Unfortunately, PBDEs are easily released from the original products, promptly reaching the environment. Knowledge about the toxicological power of these substances is still limited, which has prevented environmental and regulatory authorities from conducting adequate risk assessments. This research addresses the genotoxic and mutagenic potential of PBDEs. The effects of HepG2 cells and Salmonella typhimurium exposure to six main representatives of PBDEs, namely tetrabromodiphenyl ether (BDE-47), pentabromodiphenyl ether (BDE-99 and BDE-100), hexabromodiphenyl ether (BDE-153 and BDE-154) and decabromodiphenyl ether (BDE-209), were evaluated. The comet assay revealed that all the assessed BDEs exerted genotoxic effects but induced no micronuclei formation in HepG2 cells. These BDEs had no significant mutagenic effects on the Salmonella typhimurium strains TA98 and TA100. Taken together, the results of the genomic instability assays showed that PBDEs can represent a risk to the health of directly and indirectly exposed population, because the assessed BDEs induce genotoxic effects in the HepG2 cell line.

Mammalian toxicology and human exposures to the flame retardant 2,2',6,6'-tetrabromo-4,4'-isopropylidenediphenol (TBBPA): implications for risk assessment.

The compound 2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol (tetrabromobisphenol A, TBBPA) is used as a reactive and additive flame retardant. This review evaluates the mammalian toxicology of TBBPA and summarizes recent human exposure and risk assessments. TBBPA has a low potential for systemic or reproductive toxicity, and no-observed-adverse-effect-levels were greater than 1,000 mg/kg body weight (bw)/day in a 90-day oral toxicity study, a developmental toxicity study and a two-generation reproductive and developmental toxicity study. Some interactions of TBBPA with hormone-mediated pathways were noted in vitro; however, when studied in vivo, TBBPA did not produce adverse effects that might be considered to be related to disturbances in the endocrine system. Therefore, in accordance with internationally accepted definitions, TBBPA should not be considered an "endocrine disruptor." Furthermore, TBBPA is rapidly excreted in mammals and therefore does not have a potential for bioaccumulation. Measured concentrations of TBBPA in house dust, human diet and human serum samples are very low. Daily intakes of TBBPA in humans were estimated to not exceed a few ng/kg bw/day. Due to the low exposures and the low potential for toxicity, margins of exposures for TBBPA in the human population were between 6 × 10(4) (infants) to 6 × 10(7) (adults). Exposures of the general population are also well below the derived-no-effect-levels derived for endpoints of potential concern in REACH.

Polybrominated diphenyl ether congener (BDE-100) induces mitochondrial impairment.

Brominated flame retardants are used in various consumer products to increase their resistance to fire and/or high temperatures. Polybrominated diphenyl ethers (PBDEs) are representatives of this class and among the most widely used congeners, and BDE-100 is produced on a large scale. There is a lack of toxicological data about these compounds, which has recently become a matter of concern to the scientific community. The mitochondria are recognized as the main energy-producing organelles, as well as playing a vital role in the maintenance of many cell functions. Therefore, mitochondria were used in the present work as an experimental model to evaluate the effects of the BDE-100 congeners at concentrations ranging from 0.1 µM to 50 µM. The results showed that high concentrations of BDE-100 were able to induce mitochondrial alterations. It was observed that the substance had an affinity for the hydrophilic portion of the mitochondrial membrane, as monitored by ANS, inhibiting the glutamate + malate-stimulated mitochondrial respiration and also inducing dissipation of the mitochondrial membrane potential, deregulation of calcium homoeostasis and mitochondrial swelling, the latter being insensitive to cyclosporin A (CsA) but partially inhibited by Ruthenium Red and N-ethyl maleimide. In addition, a significant reduction in mitochondrial ATP content was found, but on the other hand, no oxidative stress was observed after exposure of the mitochondria to BDE-100. These results show the key role of mitochondria in the cytotoxicity induced by BDE-100.

BDE-99 congener induces cell death by apoptosis of human hepatoblastoma cell line - HepG2.

Polybrominated Diphenyl Ethers (PBDEs) are an important class of flame retardants with a wide range of toxic effects on biotic and abiotic systems. The toxic mechanisms of PBDEs are still not completely understood because there are several different congeners with different chemical and biological characteristics. BDE-99 is one of these, widely found in the environment and biological samples, showing evidence of neurotoxic and endocrine disruption activities, but with little information about its action mechanism described in the current literature. This work investigated the effects of BDE-99 on the HepG2 cell line in order to clarify its toxic mechanism, using concentrations of 0.5-25 µM (24 and 48 h). Our results showed that BDE-99 could cause cell death in the higher concentrations, its activity being related to a decrease in mitochondrial membrane potential and an accumulation of ROS. It was also shown that BDE-99 induced the exposure of phosphatidylserine, caspases 3 and 9 activation and DNA fragmentation in HepG2 cells, without causing the release of LDH. Thus it was shown that BDE-99 could cause HepG2 cell death by apoptosis, suggesting its toxicity to the human liver.

Estudio preliminar sobre los niveles de exposición a PBDES en sangre y leche materna en México / Exposure levels of PBDES in blood and breast milk in Mexico, a preliminary study

Los retardantes de flama bromados han sido muy usados en las últimas décadas en muchos productos de consumo. Su producción, uso, lipofilicidad y persistencia, los han vuelto contaminantes ambientales ubicuos. Han sido detectados en el ser humano en varios países y poco se conoce sobre susefectos tóxicos. El propósito de este estudio fue determinar de manera preliminar los niveles de exposición a difeniléteres polibromados (PBDEs) en la población mexicana. Se tomaron muestras de sangre a 5 mujeres de una zona urbana y muestras de leche materna a 7 de una zona rural. Los niveles de PBDEs en las mujeres de la zona urbana fueron de 21.5-37.5 ng/glípido y los de las mujeres rurales fueron 0.8-5.4 ng/g lípido.

The brominated flame retardants have been used in the last decades inmany products. Their production, use, lipofilicity and persistence, make them ubiquituos in the environment. They have been detected in humans in several countries and little is known about their toxics effects. The aim of this pilot study was to determine exposure levels of polybrominated diphenylethers (PBDEs) in the Mexican population, blood samples were taken from five women living in an urban area, whereas breast milk samples were collected from seven rural women. The levels of PBDEs in theurban area were 21.5-37.5 ng/g lipid; whereas milk concentrations in rural women were 0.8-5.4 ng/glipid.