Concentration of Tetrabromobisphenol-A in fish: systematic review and meta-analysis and probabilistic health risk assessment

Introduction

Environment contamination [1], [2], [3], [4], including food [5], [6], [7], [8], [9], [10], has increased over decades [11], [12], [13]. These pollutants include microbes [14], [15], [16], mycotoxins, pesticides, and heavy metals, causing various diseases [17]. Brominated flame retardants (BFRs) constitute the largest group of flame retardants in the market due to their low cost and high efficiency, making them highly effective in increasing fire resistance [18], [19], [20]. BFRs are added either through by chemical bonding or as additives in the manufacture of various polymer materials and serve as raw materials for different industries [19], [20], [21], [22], [23]. Among the BFRs, Tetrabromobisphenol A (TBBP-A) is widely used as a reactive flame retardant (about 90 %) in microelectronic applications such as printed circuit boards, and is rarely used as an additive in the production of acrylonitrile butadiene styrene resins [20], [24], [25], [26].

The highest consumption of this compound occurs in Asia; primarily because most electronic items using circuit boards are produced in this region [24]. Long-term use has led to its presence in various environmental matrices including water, soil, air, dust, sediments, sewage sludge, marine and terrestrial organisms, albeit in low concentrations. Subsequently, it enters the food chain through different routes during production, use, and disposal [23], [24], [25], [26]. The European Commission (EU/118/2014) has recognized these compounds as potential food contaminants, prompting EU member states to investigate their occurrence in food [18]. However, due to its high lipophilicity, transferability to recovery products, bioaccumulation, and chemical stability, it is known as a stable emerging micropollutant in the environment [27]. High consumption of TBBPA can potentially have negative effects on humans and the environment, especially in aquatic environments [24].

Exposure to TBBP-A may result in endocrine disruption, immunotoxicity, neurotoxicity, carcinogenicity, negative reproductive and developmental effects, and long-term consequences, including effects on the second generation [20], 23], 25], 27], 28]. Consequently, TBBP-A has been classified as a carcinogen (Group 2A) by the World Health Organization [29].

The two primary modes of human exposure to TBBP-A are through diet and dust inhalation [19], 21], 23], 28]. Diet, especially seafood consumption, is the main route of human exposure to some BFRs, whose metabolites have also been found in marine organisms and human breast milk. TBBP-A has been detected in low concentrations in various marine organisms, including mollusks, crabs, fish, and porpoises collected from the North Sea [25].

Wang et al. conducted a study in China in 2013 regarding the presence of TBBP-A in food including fish/seafood. This pollutant was detected in only 39 % of all analyzed foods. In fish and seafood, TBBP-A was found in only 5 of 18 samples, with an average concentration of 6.01 ng/g [23].

In 2016, TBBP-A levels were evaluated in 115 samples across 9 food categories in Korean markets, indicating higher contamination levels in fish and cephalopods compared to other food items [30]. Similarly, in 2019, the levels of TBBP-A were evaluated in 24 samples of wild fish and seafood and 16 samples of farmed bivalve mollusks from the western Mediterranean Sea, all registering levels were below the LOQ of 0.05 ng/g fw [31]. Another study in European markets in 2016 evaluated the concentration of halogenated flame retardants, including TBBP-A, in commercial seafood, with 90.5 % of the products showing contamination. The maximum concentration of TBBP-A was reported as 48.6 ng/g lw [32].

In the UK, among 156 food samples collected, TBBP-A was detected above the LOD only in a few processed food samples with low contamination levels (0.01–0.15 ng/g whole weight) [33].

A study in the coastal areas of Bohai Sea, China, studied the distribution patterns and nutritional transfer properties of TBBP-A/S and its analogs in 97 biological samples (including 5 species of phycophyta, 2 species of zooplankton, 14 species of invertebrates, and 13 species of fish). The concentration of TBBP-A and analogs ranged from not detected (ND) to 2782.8 ng/g lipid weight (LW) [25]. In recent years, several review articles have been published on the pollutant TBBP-A, encompassing its presence in consumer goods, various environments (such as sediments, surface water, soil, sewage sludge, indoor and outdoor air, and indoor dust), as well as in a variety of biological samples and the food chain (including plants, fish, humans, birds, and invertebrates) [34], [35], [36], [37], [38].

He et al. conducted a comprehensive investigation into environmental occurrences and bioremediation methods for emerging organohalogens that TBBP-A and fish were a small part of their study [38].

Although several studies have evaluated TBBP-A concentrations in fish fillets, no systematic review study has been conducted [18], 19], 22], 26], 28], 33], 39], 40]. Therefore, the main aims of the current study were to meta-analyze the concentration of TBBP-A in fish fillets and conduct a probabilistic health risk assessment.

Materials and methods

Results

Number of studies in countries

Fourteen papers comprising 26 data-reports (sample size: 466) were included in our meta-analysis (Figure 1). The ranking of countries based on study count was South Korea (5)∼UK (5)>Czech Republic (3)∼China (3)∼Japan (3)>Belgium (1) Ireland (1)∼Netherlands (1)∼Sweden (1)∼France (1)∼Switzerland (1)∼Germany (1) (Table 1 and Figure 2).

Figure 1:

Process of section paper based on PRISMA.

Table 1:

Main characteristic included in our study.

Country	Sample number	Mean (µg/kg-ww)	SD (µg/kg-ww)	Min (µg/kg-ww)	Max (µg/kg-ww)	LOD	Method of detection	References
Czech	32	5.50E−01	1.13E−01	0.00E+00	0.00E+00	0.1–1 μg/kg	UHPLC/MS–MS	[22]
Czech	48	1.29E+00	1.07E+00	1.40E−01	4.43E+00		LC–MS/MS	[39]
South Korean	11	1.40E−01	4.58E−01	ND	1.78E+00	0.043 μg/kg	LC–MS/MS	[19]
South Korean	11	1.60E−02	3.30E−02	ND	8.90E−02	0.043 μg/kg	LC–MS/MS	[19]
South Korean	11	2.60E−02	6.70E−02	ND	2.51E−01	0.043 μg/kg	LC–MS/MS	[19]
South Korean	11	4.00E−03	1.40E−02	ND	5.30E−02	0.036 μg/kg	LC–MS/MS	[19]
South Korean	12	1.80E−02	1.08E−02			0.036 μg/kg	LC–MS/MS	[19]
Belgium	61	6.50E−02	3.00E−02			NM	UHPLC/MS–MS	[28]
Ireland	10	5.00E−03	3.00E−03			0.01 μg/kg	LC–MS/MS	[18]
UK	36	1.00E−02	1.00E−02	<0.01	<0.03	0.01	HPLC-MS/MS	[33]
China	13	2.10E−02	1.26E−02			100 pg/g Dw	HPLC-MS/MS	[25]
UK	30	9.23E−01	3.89E−01				LC-ESI-MS/MS	[40]
UK	22	2.00E−05	1.20E−05			0.00003–0.00005 µg/kg	LC–MS/MS	[21]
Japan	15	1.00E−02	6.00E−03				HRGC/HRMS	[54]
Japan	15	1.00E−02	6.00E−03				HRGC/HRMS	[54]
Japan	15	2.00E−02	1.20E−02				HRGC/HRMS	[54]
China	34	3.30E+00	6.60E−01	1.20E+00	9.00E+00	0.015 μg/kg	LC-MS	[24]
China	18	1.62E−01	3.30E−01	0.00E+00	1.14E+00	NM	UHPLC/MS–MS	[23]
Czech	15	1.39E+00	1.48E+00	1.60E−01	6.06E+00		UHPLC/MS–MS	[20]
Netherlands	7	4.05E−01	2.25E−02	3.60E−01	4.50E−01	0.1 µg/kg	LC–MS/MS	[26]
UK	4	7.05E−01	2.43E−01	2.20E−01	1.19E+00	0.1 µg/kg	LC–MS/MS	[26]
UK	7	6.65E−01	1.78E−01	3.10E−01	1.02E+00	0.1 µg/kg	LC–MS/MS	[26]
Sweden	7	1.65E−01	8.25E−02	0.00E+00	3.30E−01	0.1 µg/kg	LC–MS/MS	[26]
France	7	5.00E−01	1.30E−01	2.40E−01	7.60E−01	0.1 µg/kg	LC–MS/MS	[26]
Switzerland	7	5.00E−01	1.30E−01	2.40E−01	7.60E−01	0.1 µg/kg	LC–MS/MS	[26]
Germany	7	3.35E−01	5.75E−02	2.20E−01	4.50E−01	0.1 µg/kg	LC–MS/MS	[26]

1. SD, standard deviation; LOD, limit of detection; ND, not detected; NM, not mentioned.

Figure 2:

The number study on TBBP-A in fish based on countries.

Method of detection

The ranking of detection methods based on study count was LC–MS/MS (15) > UHPLC/MS–MS (4) > HRGC/HRMS (3) > HPLC-MS/MS (2) > LC-MS (1) ∼ LC-ESI-MS/MS (1) (Table 1 and Figure 3).

Figure 3:

The number study based on method of detection TBBP-A.

Probabilistic health risk assessment

Maximum THQ values for TBBP-A in fish were observed in China (6.69E−6), France (1.77E−6), and Czech Republic (1.24E–6) (Figure 4). Maximum CR values for TBBP-A in fish were noted in China (1.26E−8), France (3.35E−9), and Czech Republic (2.33E−9) (Figure 5). Across all countries, CR values were below 1E−6, indicating acceptable carcinogenic risk for consumers.

Figure 4:

Non-carcinogenic risk due to TBBP-A in fish based on countries subgroups.THQ shows non-carcinogenic risk (THQ=CDI/RfD).

Figure 5:

Carcinogenic risk due to TBBP-A in fish based on countries subgroups. CR shows carcinogenic risk (CR=CDI × CSF).

Discussion

It is worth noting that TBBP-A is classified as an emerging contaminant, meaning its potential environmental impacts and accumulation pathways might not be fully understood or recognized by the scientific community [24]. The absence of specific regulatory recognition or guidelines for TBBP-A in fish can lead to lower research priority [31].

Regulatory guidelines shape research priorities and allocate resources to address substance-related risks. Restricted funding or budgetary limitations can impede extensive research. Consequently, there might be relatively less emphasis on studying TBBP-A presence in fish compared to more well-established contaminants [55], [56], [57], [58]. The limited number of studies on TBBP-A in fish can indeed be attributed to factors such as low familiarity with the chemical, the newness of the pollutant, cost considerations, and the lack of recognition of its accumulation chain [59]. These factors, individually or collectively, contribute to a shortage of research specifically focusing on TBBP-A in fish.

According to research findings, the main sources of TBBP-A entering the environment are associated with the use and disposal of products that contain this flame retardant [60], 61]. Brominated flame retardants (BFRs) have diverse applications across various industries, including textiles, wiring, furniture, industrial paints, plastics, and foams [62]. Moreover, their use is prevalent in electronic products, playing a crucial role in improving fire resistance [63]. Over time, TBBP-A can migrate from these products into the surrounding environment through pathways such as wastewater discharges, landfill leachate, or atmospheric deposition [64]. Once released, TBBP-A can enter aquatic habitats through runoff or direct contact with water sources. TBBP-A can enter the aquatic environment through effluent from wastewater treatment plants (WWTPs) [65]. TBBP-A-containing wastewater, which may originate from industrial processes, residential sources, or even landfill leachate, can be discharged into aquatic habitats after treatment [66]. While WWTPs remove many contaminants, including TBBP-A, certain amounts can still be present in the effluent and enter the environment. Landfills can be another source of TBBP-A discharge into the aquatic environment [67]. TBBP-A can be present in waste materials, such as electronic waste, disposed of in landfills. Over time, rainfall or leachate from the landfill can carry TBBP-A into surrounding soil and water sources, potentially leading to its entry into aquatic ecosystems [68]. Regarding the accumulation of TBBP-A in fish tissues, certain flame retardants, including TBBP-A, have the potential to bioaccumulate in organisms. Fish can be exposed to TBBP-A through water or by ingesting contaminated prey. Once absorbed, TBBP-A can accumulate in fish tissues, particularly in fatty tissues, over time. However, as reported by Ashizuka et al., there was no correlation between TBBP-A and fat content in any region. This lack of correlation may be attributed to the chemical characteristics of TBBP-A, which has a phenolic structure, and its rapid metabolic conversion within the body [54]. The study of Driffield et al. found no detectable levels of TBBP-A above the limit of detection, which was as low as 0.05 mg kg^–1. This is likely because TBBP-A forms strong chemical bonds with the polymer matrix during the manufacturing process, minimizing its potential for leaching. Moreover, since the levels of these flame retardants in the shellfish samples were similar, it was concluded that exposure to these brominated flame retardants (BFRs) through shellfish consumption is not considered significant compared to exposure from other dietary sources [21]. Chen et al. and Gong et al. conducted studies revealing significant bioaccumulation of TBBP-A in lower trophic levels, specifically in Tigriopus japonicus, a type of zooplankton. The bioaccumulation factor was high, indicating substantial accumulation of TBBP-A in these organisms [69], 70].

The majority of analytical methods for halogenated flame retardants, such as TBBP-A, involve liquid chromatographic (LC) separation combined with mass spectrometric (MS) or optical detection techniques [71]. LC–MS can easily detect polar analytes such as TBBP-A and/or hydroxylated BFRs, which typically necessitate derivatization prior to GC analysis [72]. LC-MS is more commonly used than conventional methods for measuring TBBP-A concentrations in fish due to its higher sensitivity, selectivity, structural confirmation capabilities, and established methods [26]. These advantages make LC-MS a reliable and efficient technique for assessing TBBP-A contamination in fish and understanding associated risks. LC-ESI-MS/MS, a powerful analytical technique combining liquid chromatography with electrospray ionization and tandem mass spectrometry, is relatively less commonly used for TBBP-A analysis in fish [22]. As Fernandes et al., have mentioned, analyzing compounds such as BDE-209 and DBDPE necessitates meticulous attention to ensuring clean contact surfaces throughout the entire process, including the injector, GC column, transfer lines, and MS sources [33]. Additionally, it is crucial to have a thorough understanding and precise control of the temperatures at which degradation of these compounds may initiate. In the ICP-MS system employed for bromine measurement, the internal transfer lines are not typically under the direct control of the operator, which may lead to the possibility of adsorption occurring [33].

Liu et al. attempted to analyze TBBP-A-BAE and TBBP-A-BDBPE using Agilent Technologies (6460 Triple Quadrupole MS/MS) and Waters (Quattro Ultima Triple Quadrupole MS/MS) with APCI-MS. However, the MS signals obtained were very low. To address this issue, the pretreatment method was optimized. In previous studies, HPLC coupled with a UV detector was utilized for the analysis of TBBP-A-BAE and TBBP-A-BDBPE. In Liu et al. study, HPLC-DAD (High-Performance Liquid Chromatography with Diode Array Detection) was employed, enabling the complete separation of 209 TBBP-A-BAE and TBBP-A-BDBPE from other interfering peaks [25].

This finding suggests a significant presence of TBBP-A contamination in fish from Chinese waters, likely due to industrial activities and potential improper waste management practices. China has become the largest importer of e-waste in the world, which has led to heightened public concerns regarding the significant release of hazardous materials, including brominated flame retardants, into the environment [73]. This release occurs during the dismantling of e-waste, improper disposal practices, and inadequate recycling processes. As mentioned by Okeke et al., the available data suggests that the main sources of TBBP-A in China are associated with primitive e-waste dismantling methods, TBBP-A manufacturing, and the processing of TBBP-A-based materials [66]. For example, the Pearl River Delta (PRD) region in China is recognized as a prominent center for the electronics industry, where chemicals like DBDPE and TBBP-A-DBPE are extensively utilized [74]. Consequently, As reported by He et al., the high concentrations of these substances found in the region are consistent with their widespread usage in electronic products [24]. Similarly, another study identified elevated TBBP-A concentrations in fish samples obtained from the Bohai Sea, an important fishing region in China. The study suggested that the high TBBP-A levels in fish were linked to industrial and municipal wastewater discharges, as well as atmospheric deposition [25]. These findings emphasize the possibility of TBBP-A contamination in fish from specific regions in China where industrial activities and inadequate waste management practices may contribute to the presence of this flame retardant in aquatic environments. The concentration of TBBP-A can vary among different fish species. This variation can be influenced by factors such as the species’ feeding habits, habitat, and position in the food chain [75]. Some fish species may have higher levels of TBBP-A due to their feeding patterns or their exposure to contaminated environments, while others may have lower levels. For example, predatory fish higher up in the food chain, such as shark, swordfish, and large tuna species (e.g., bluefin tuna), have been found to have higher levels of TBBP-A. This is because they consume other fish containing TBBP-A, and the contaminants can accumulate and biomagnify as they move up the food chain.

The findings from the study conducted by Ashizuka et al. in Japan support the idea that TBBP-A has low bioavailability and can be easily metabolized within the organism. In a separate investigation by the Ministry of Health, Labor and Welfare of Japan, it was estimated that the average daily fish consumption per person in Japan is approximately 82.2 g. Based on this estimation, the study calculated the daily intake from fish to be 0.58 ng per kilogram of body weight (ng/kg bw/day) for TBBP-A, assuming a body weight of 50 kg. Therefore, the contamination level in fish was generally not regarded as a significant issue [54].

THQ in the all countries was below than 1, hence consumers are at an acceptable non-carcinogenic risk. In the case of TBBP-A in fish from China, the maximum THQ value indicates that the estimated exposure dose of TBBP-A through fish consumption in China exceeded the reference dose, raising potential health concerns. This suggests that the levels of TBBP-A in fish from China may pose a greater risk to human health compared to other countries where TBBP-A contamination in fish has been assessed. The risk of TBBP-A exposure in China can potentially be influenced by two factors: per capita consumption of fish and the concentration of TBBP-A in fish. China has a notable tradition of consuming fish due to its large population and cultural dietary preferences [76]. Chinese cuisine has a long-standing tradition of incorporating fish as a prominent source of protein, and the per capita consumption of fish varies across different regions in China. It is worth noting that THQ values are influenced by various factors, including the concentration of the contaminant, the consumption rate of fish, and the specific reference dose used in the assessment [76].

The markedly lower levels of carcinogenic and non-carcinogenic risks compared to the standard limits suggest that the low concentration of TBBP-A, coupled with its low toxicity, is the primary reason behind this observation. In addition to the low concentration of TBBP-A and its low toxicity, several other factors can contribute to the decrease in carcinogenic and non-carcinogenic risks associated with it. These factors include the various pathways of exposure to TBBP-A, such as inhalation or dermal contact. Effective risk management practices, such as the implementation of regulatory controls and monitoring programs, also play a crucial role in reducing risks. Moreover, individuals’ dietary habits and consumption patterns, such as opting for fish with lower TBBP-A levels or reducing fish consumption frequency, can impact their exposure levels. Additionally, environmental factors, such as pollution control measures and stringent regulations, have the potential to influence the levels of TBBP-A in the environment and consequently in fish.

Conclusions

This study aimed to gather and analyze existing research on TBBP-A in fish through a systematic search. The concentration of TBBP-A in fish was meta-analyzed and health risk assessments were estimated by the MCS method. The studies conducted in China and the Czech Republic indicated significantly higher TBBP-A levels compared to other countries. Consequently, it is imperative to conduct more studies and implement programs aimed at reducing emission sources in these specific regions.

The risk assessment revealed that both carcinogenic and non-carcinogenic risks associated with TBBP-A in China and France are higher compared to other countries. However, overall, the carcinogenic and non-carcinogenic risks across all countries fall within acceptable ranges. Hence, it is recommended to conduct similar studies in diverse countries to comprehensively determine the health implications of TBBP-A in marine foods.