F-53B mediated ROS affects uterine development in rats during puberty by inducing apoptosis.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as pollutants, can cause palpable environmental and health impacts around the world, as endocrine disruptors, can disrupt endocrine homeostasis and increase the risk of diseases. Chlorinated polyfluoroalkyl ether sulfonate (F-53B), as a substitute for PFAS, was determined to have potential toxicity. Puberty is the stage when sexual organs develop and hormones change dramatically, and abnormal uterine development can increase the risk of uterine lesions and lead to infertility. This study was designed to explore the impact of F-53B on uterine development during puberty. Four-week-old female SD rats were exposed to 0.125 and 6.25 mg/L F-53B during puberty. The results showed that F-53B interfered with growth and sex hormone levels and bound to oestrogen-related receptors, which affected their function, contributed to the accumulation of reactive oxygen species, promoted cell apoptosis and inhibited cell proliferation, ultimately causing uterine dysplasia.

Angiotoxic effects of chlorinated polyfluorinated ether sulfonate, a novel perfluorooctane sulfonate substitute, in vivo and in vitro.

Chlorinated polyfluorinated ether sulfonate (Cl-PFESA), a substitute for perfluorooctane sulfonate (PFOS), has been widely used in the Chinese electroplating industry under the trade name F-53B. The production and use of F-53B is keep increasing in recent years, consequently causing more emissions into the environment. Thus, there is a growing concern about the adverse effects of F-53B on human health. However, related research is very limited, particularly in terms of its toxicity to the vascular system. In this study, C57BL/6 J mice were exposed to 0.04, 0.2, and 1 mg/kg F-53B for 12 weeks to assess its impact on the vascular system. We found that F-53B exposure caused aortic wall thickening, collagen deposition, and reduced elasticity in mice. In addition, F-53B exposure led to a loss of vascular endothelial integrity and a vascular inflammatory response. Intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were found to be indispensable for this process. Furthermore, RNA sequencing analysis revealed that F-53B can decrease the repair capacity of endothelial cells by inhibiting their proliferation and migration. Collectively, our findings demonstrate that F-53B exposure induces vascular inflammation and loss of endothelial integrity as well as suppresses the repair capacity of endothelial cells, which ultimately results in vascular injury, highlighting the need for a more thorough risk assessment of F-53B to human health.

Comparative Toxicological Effects of Perfluorooctane Sulfonate and Its Alternative 6:2 Chlorinated Polyfluorinated Ether Sulfonate on Earthworms.

High levels of 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), which is a substitute for perfluorooctane sulfonate (PFOS), are detected in various environmental matrices, wildlife, and humans. Chlorinated polyfluorinated ether sulfonate has received increased attention due to its potential risk to ecosystems. However, its toxicity in the soil organisms remains unclear. In the present study, a comparative investigation was conducted on the toxicities of 6:2 Chlorinated polyfluorinated ether sulfonate (F-53B) and PFOS to the earthworm Eisenia. fetida. F-53B was significantly more acutely toxic to earthworms than PFOS, with median lethal concentrations of 1.43 and 1.83 mmol/kg dry soil (~816 and 984 mg/kg dry soil), respectively. Although both F-53B and PFOS, at 0.4 mmol/kg dry soil (=228 and 215 mg/kg dry soil) caused oxidative stress in earthworms, as evidenced by increased superoxide dismutase, peroxidase, and catalase activities as well as malondialdehyde level, the stress caused by F-53B was higher than that caused by PFOS. In transcriptomic and metabolomic studies, negative effects of PFOS and F-53B were observed on several metabolic processes in earthworms, including protein digestion and amino acid absorption, lipid metabolism, and the immune response. Compared with PFOS, F-53B exhibited a weaker disruption of lipid metabolism, comparable potency for toxicity to the immune response, and a stronger potency in extracellular matrix destruction along with apoptosis and ferroptosis induction. Hence, our data suggest that F-53B is more toxic than PFOS to earthworms. The findings provide some new insights into the potential toxicity of F-53B to soil organisms. Environ Toxicol Chem 2024;43:170-181. © 2023 SETAC.

Interactive effects of polystyrene nanoplastics and 6:2 chlorinated polyfluorinated ether sulfonates on the histomorphology, oxidative stress and gut microbiota in Hainan Medaka (Oryzias curvinotus).

Nanoplastics adsorb surrounding organic contaminants in the environment, which alters the physicochemical properties of contaminants and affects associated ecotoxicological effects on aquatic life. The current work aims to explore the individual and combined toxicological implications of polystyrene nanoplastics (80 nm) and 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFAES, trade name: F-53B) in an emerging freshwater fish model Hainan Medaka (Oryzias curvinotus). Therefore, O. curvinotus were exposed to 200 µg/L of PS-NPs or 500 µg/L of F-53B in the single or mixture exposure for 7 days to investigate the effects on fluorescence accumulation, tissue damage, antioxidant capacity and intestinal flora. The PS-NPs fluorescence intensity was significantly higher in the single exposure treatment than it in combined exposure treatment (p < 0.01). Histopathological results showed that exposure to PS-NPs or F-53B inflicted varying degree of damages to the gill, liver, and intestine, and these damage were also present in the corresponding tissues of the combined treatment group, illustrating a stronger extent of destruction of these tissues by the combined treatment. Compared to the control group, combined exposure group elevated the malondialdehyde (MDA) content, superoxide dismutase (SOD) and catalase (CAT) activities except in the gill. In addition, the adverse contribution of PS-NPs and F-53B on the enteric flora in the single and combined exposure groups was mainly characterised in the form of reductions in the number of probiotic bacteria (Firmicutes) and this reduction was aggravated by the combined exposure group. Collectively, our results indicated that the toxicological effects of PS-NPs and F-53B on pathology, antioxidant capacity and microbiomics of medaka may be modulated by the interaction of two contaminants with mutually interactive effects. And our work offers fresh information on the combined toxicity of PS-NPs and F-53B to aquatic creatures along with a molecular foundation for the environmental toxicological mechanism.

Performance of Green Surfactants in the Formulation of Heavy-Duty Laundry Liquid Detergents (HDLD) with Special Emphasis on Palm Based Alpha Methyl Ester Sulfonates (α-MES).

Liquid detergent has an increasing demand in North America, Western Europe, and Southeast Asia countries owing to its convenience to use and efficiency to clean. Alpha methyl ester sulfonates (α-MES), an anionic surfactant derived from palm oil based methyl ester, was reported to have lower manufacturing cost, good detergency with less dosage, excellent biodegradability, higher tolerance to hard water, and lower eco-toxicity as compared to linear alkylbenzene sulfonates (LABS). LABS was known as the workhorse of the detergent industry in the 20th century. Although palm-based α-MES was successfully used as the sole surfactant in powder detergent, there are still some unsettled technical issues related to phase stability and viscosity when using this anionic surfactant in heavy-duty laundry liquid detergent formulations. This paper will review not only the market overview of detergents, the application and performance of green surfactants in laundry detergents but also will highlight the technical issues related to the application of palm-based α-MES in laundry liquid detergent and some of the possible methods to overcome the formulation adversities.

Polystyrene microplastics decrease F-53B bioaccumulation but induce inflammatory stress in larval zebrafish.

There is growing concern that microplastics (MPs), which act as carriers of other organic contaminants, are mistakenly ingested by aquatic organisms, consequently causing unpredictable adverse effects. In this study, zebrafish larvae (6 d post fertilization) were exposed to either 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), polystyrene microplastics (PS-MPs) or their combination for 7 d to evaluate the effects of the presence of PS-MPs on the bioaccumulation and immunomodulation of F-53B. PS-MPs greatly promoted the sorption of F-53B, which reduced the bioavailability and bioaccumulation of F-53B in zebrafish larvae. F-53B, PS-MPs, or their mixture significantly reduced the body weight of zebrafish larvae. Combined exposure of PS-MPs and F-53B resulted in a significant reduction in superoxide dismutase (SOD) and lysozyme activity, indicating the occurrence of oxidative stress and inflammatory response in zebrafish larvae. The content of malondialdehyde (MDA) and immunoglobulin M (IgM) was not affected by F-53B or PS-MPs, but significantly increased in their combined exposure. Furthermore, co-exposure of F-53B and PS-MPs significantly upregulated the transcripts of pro-inflammatory cxcl-clc and il-1ß genes and increased the levels of iNOS protein in zebrafish larvae. In addition, enhanced protein expression of NF-κB paralleled the upregulation in the expression of most immune-related genes, suggesting NF-κB pathway was mechanistically involved in these responses. Collectively, the presence of MPs decreased F-53B bioaccumulation, but induced inflammatory stress in larval zebrafish. These findings highlight the health risks of co-contamination of MPs and F-53B in aquatic environments.

Subchronic exposure of environmentally relevant concentrations of F-53B in mice resulted in gut barrier dysfunction and colonic inflammation in a sex-independent manner.

F-53B (6:2 chlorinated polyfluorinated ether sulfonate) is currently recognized as a safe alternative to long-chain PFASs in China. However, an increasing number of studies have recently authenticated its biotoxicological effects. In this study, for evaluating the gut toxicity of F-53B in mammals, both female and male mice were orally exposed to 0, 1, 3, or 10 µg/L F-53B for 10 weeks. Our results showed that F-53B significantly accumulated in the colon, ileum and serum when exposed to 10 µg/L F-53B for 10 weeks. F-53B exposure not only increased the transcriptional levels of ion transport-related genes but could also interact with the CFTR protein directly. Interestingly, subchronic F-53B exposure also increased the transcription of mucus secretion-related genes, but the protein level of Muc2 decreased after F-53B exposure, indicating that there was a compensatory phenomenon after mucus barrier injury. Furthermore, F-53B exposure also induced colonic inflammation associated with gut microbiota dysbiosis in the colon. Taken together, our results indicated that the potential gut toxicity of F-53B and almost all of the changed parameters were significantly affected in both female and male mice, suggesting that F-53B could disturb the gut barrier without sex dependence in mice.

Acute exposure to environmentally relevant concentrations of Chinese PFOS alternative F-53B induces oxidative stress in early developing zebrafish.

6:2 chlorinated polyfluorinated ether sulfonate (F-53B), a Chinese PFOS alternative, has recently been identified in the aquatic environment at concentrations similar to or higher than perfluorooctane sulfonate (PFOS). Although previous studies have shown that F-53B can trigger oxidative stress in fish, the underlying molecular mechanism is still largely unknown. In this study, zebrafish embryos were exposed to various concentrations of F-53B (0, 0.5, 20 and 200 µg/L) for 5 d to investigate oxidative stress responses and possible molecular mechanisms of action. Our results showed that F-53B accumulated in a concentration-dependent manner in zebrafish larvae. The contents of malondialdehyde (MDA) and reduced glutathione (GSH), as well as the activities, mRNA and protein levels of most of antioxidant enzyme genes involved in the phosphatidylinositol 3-kinase (PI3K)/Akt/Nrf2-ARE pathway were significantly reduced. Further in silico study indicated that F-53B binds tightly to PI3K, which may be related to the inhibition of Nrf2-regulated antioxidant functions by F-53B as a PI3K inhibitor. Combining in vivo and in silico studies, we elucidated the effects of F-53B on antioxidant system of zebrafish through the PI3K/Akt/Nrf2-ARE pathway, which increases our understanding of the molecular mechanism of F-53B on antioxidant responses in fish.

Chronic exposure to 6:2 chlorinated polyfluorinated ether sulfonate acid (F-53B) induced hepatotoxic effects in adult zebrafish and disrupted the PPAR signaling pathway in their offspring.

As a Chinese-specific alternative to perfluorooctane sulfonate (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (commercial name: F-53B) has been used in the metal plating industry for over 40 years. This prevalence of use has resulted in its subsequent detection within the environment, wildlife, and humans. Despite this, however, its hepatotoxic effects on aquatic organisms remain unclear. Here, we characterized the impacts of long-term F-53B exposure on adult zebrafish liver and their offspring. Results showed that the concentration of F-53B was greater in the F0 liver than that in the gonads and blood. Furthermore, males had significantly higher liver F-53B levels than females. Hepatomegaly and obvious cytoplasmic vacuolation indicated that F-53B exposure induced liver injury. Compared to control, liver triglyceride levels decreased by 30% and 33.5% in the 5 and 50 µg/L-exposed males and 22% in 50 µg/L-exposed females. Liver transcriptome analysis of F0 adult fish found 2175 and 1267 differentially expressed genes (DEGs) in the 5 µg/L-exposed males and females, respectively. Enrichment analyses further demonstrated that the effects of F-53B on hepatic transcripts were sex-dependent. Gene Ontology showed that most DEGs were involved in multicellular organism development in male fish, whereas in female fish, most DEGs were related to metabolic processes and gene expression. qRT-PCR analysis indicated that the PPAR signaling pathway likely contributed to F-53B-induced disruption of lipid metabolism in F0 adult fish. In F1 larvae (5 days post fertilization), the transcription of pparα increased, like that in F0 adult fish, but most target genes showed the opposite expression trends as their parents. Taken together, our research demonstrated chronic F-53B exposure adversely impacts zebrafish liver, with disruption of PPAR signaling pathway dependent on sex and developmental stage.

Parental exposure to 6:2 chlorinated polyfluorinated ether sulfonate (F-53B) induced transgenerational thyroid hormone disruption in zebrafish.

Although 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), an alternative to perfluorooctanesulfonate (PFOS), has been regularly detected in different environmental matrices, information regarding its toxicity remains limited. To explore the transgenerational thyroid-disrupting capacity of F-53B, adult zebrafish (F0) were exposed to different concentrations of F-53B (0, 5, 50, or 500µg/L) for 180d, with their offspring (F1 and F2) subsequently reared in uncontaminated water. Thyroid disturbances were then examined in the three (F0, F1, and F2) generations. For F0 adult fish, thyroxine (T4) increased in both sexes after exposure to 50µg/LF-53B, whereas 3,5,3'-triiodothyronine (T3) decreased in all groups, except for 50µg/LF-53B-treated males. For F1 embryos, parental exposure resulted in F-53B transfer as well as an increase in T4 content. At 5days post-fertilization, the significant increase in T4 and decrease in T3 were accompanied by a decrease in body length, increase in mortality, and increase in uninflated posterior swim bladder occurrence in F1 larvae. Although thyroid hormone levels were not changed significantly in F1 adult fish or F2 offspring compared with the control, the transcription levels of several genes along the hypothalamus-pituitary-thyroid axis were significantly modified. Our study demonstrated that F-53B possesses transgenerational thyroid-disrupting capability in zebrafish, indicating it might not be a safer alternative to PFOS.

Toxicokinetics and toxic effects of a Chinese PFOS alternative F-53B in adult zebrafish.

6:2 chlorinated polyfluorinated ether sulfonate (F-53B), a Chinese PFOS alternative, has recently been identified in river water, sewage sludge, wildlife and humans, causing great concerns about its potential toxic effects. Here, we report the first investigation of the toxicokinetics and oxidative stress of F-53B in adult zebrafish. Adult male and female zebrafish were exposed to 10 and 100 µg/L of F-53B for 7 days followed by a 5-d depuration period to examine bioaccumulation, distribution, and depuration of F-53B in fish. The results showed that F-53B was readily accumulated in fish tissues with log BCF values of 2.36-3.65, but was eliminated slowly (t1/2 = 152.4-358.5 h). F-53B accumulation was greater in males than in females and the concentration in tissues decreased in the following order: gonad ≈ liver ≫ gill ≫ brain in females and liver ≈ gill ≫ gonad ≫ brain in males, showing sex- and tissue- specific accumulation of F-53B in fish. After chronic exposure to F-53B for 28 days, a significant dose-dependent increase in histopathological changes in the liver were mainly manifested by vacuolation. Furthermore, F-53B also significantly reduced the enzyme activity (or content) of most of the measured oxidative stress-related markers (e.g., SOD, CAT and MDA) except for an increase in GSH-Px activity, indicating that oxidative stress was induced in zebrafish after treatment with F-53B. The results of this study provide important information on the toxicokinetics and toxic effects of F-53B, which will contribute to the ecological risk assessments of F-53B released into surface waters.

Optical Control of Metal Ion Probes in Cells and Zebrafish Using Highly Selective DNAzymes Conjugated to Upconversion Nanoparticles.

Spatial and temporal distributions of metal ions in vitro and in vivo are crucial in our understanding of the roles of metal ions in biological systems, and yet there is a very limited number of methods to probe metal ions with high space and time resolution, especially in vivo. To overcome this limitation, we report a Zn2+-specific near-infrared (NIR) DNAzyme nanoprobe for real-time metal ion tracking with spatiotemporal control in early embryos and larvae of zebrafish. By conjugating photocaged DNAzymes onto lanthanide-doped upconversion nanoparticles (UCNPs), we have achieved upconversion of a deep tissue penetrating NIR 980 nm light into 365 nm emission. The UV photon then efficiently photodecages a substrate strand containing a nitrobenzyl group at the 2'-OH of adenosine ribonucleotide, allowing enzymatic cleavage by a complementary DNA strand containing a Zn2+-selective DNAzyme. The product containing a visible FAM fluorophore that is initially quenched by BHQ1 and Dabcyl quenchers is released after cleavage, resulting in higher fluorescent signals. The DNAzyme-UCNP probe enables Zn2+ sensing by exciting in the NIR biological imaging window in both living cells and zebrafish embryos and detecting in the visible region. In this study, we introduce a platform that can be used to understand the Zn2+ distribution with spatiotemporal control, thereby giving insights into the dynamical Zn2+ ion distribution in intracellular and in vivo models.

Two-generational reproductive toxicity assessment of 6:2 chlorinated polyfluorinated ether sulfonate (F-53B, a novel alternative to perfluorooctane sulfonate) in zebrafish.

As an alternative to perfluorooctane sulfonate (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (commercial name: F-53B) has been used in the Chinese chrome plating industry for over four decades. It has been increasingly detected in environmental matrices in recent years, causing great concern regarding its potential health risks to humans and wildlife. However, its adverse effects on biota remain largely unknown. To explore the chronic toxicity of F-53B on reproduction, a two-generational study was conducted using zebrafish (Danio rerio). Adult zebrafish (F0 generation) were chronically exposed to different concentrations of F-53B (0, 5, 50, and 500 µg/L) for 180 d using a flow-through exposure system, with F1 and F2 generations reared without exposure. The reproductive toxicity endpoints were assessed in F0 and F1 adult fish. Results showed that F-53B accumulated in the F0 gonads and transferred to the F1 generation via maternal eggs, and even remained in F1 adult fish and their eggs (F2) after 180 d depuration. In the F0 generation, F-53B exposure significantly inhibited growth and induced reproductive toxicity, including decreased gonadosomatic index and egg production/female, changes in the histological structure of the gonads, and increased serum testosterone levels. In particular, serum estradiol and vitellogenin levels were significantly increased in 5 µg/L F-53B-exposed adult males. The transcriptional levels of several genes along the hypothalamic-pituitary-gonadal axis were altered in F0 generation fish. Testis transcriptome analysis revealed that F-53B exposure disrupted spermatogenesis in F0 male zebrafish. Maternal transfer of F-53B also induced adverse effects on growth and reproduction in the F1 generation. Furthermore, the higher occurrence of malformation and lower survival in F1 and F2 embryos indicated that parental exposure to F-53B could impair the embryonic development of offspring. Taken together, this study demonstrated that F-53B could induce reproductive toxicity in zebrafish similar to that induced by legacy PFOS, and its potential adverse effects on offspring deserve further investigation.

Subchronic reproductive effects of 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFAES), an alternative to PFOS, on adult male mice.

With a similar structure to perfluorooctane sulfonate (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFAES) has been widely used as a mist suppressant in the chromium plating industry in China since the 1970s. After being disregarded for the past 30 years, 6:2 Cl-PFAES has now been detected in environmental matrices and human sera, suggesting potential health concerns. We carried out a subchronic exposure study to investigate the reproductive toxicity of 6:2 Cl-PFAES exposure (0, 0.04, 0.2, and 1.0 mg/kg/d body weight, 56 d) in adult male BALB/c mice. Results showed that relative epididymis and testis weights decreased in the 1.0 mg/kg/d group compared with the control. However, no changes were observed in the serum levels of testosterone, estradiol, follicle-stimulating hormone (FSH), or luteinizing hormone (LH), nor in the histopathological structure of the epididymis and testis and sperm count. In addition, 56 d of consecutive gavage of 1.0 mg/kg/d of 6:2 Cl-PFAES did not affect male mouse fertility. RNA sequencing showed that no genes were significantly altered in the testes after 6:2 Cl-PFAES exposure. Several testicular genes, which are sensitive to PFOS exposure, were also detected using Western blotting, and included steroidogenic proteins, STAR, CYP11A1, CYP17A1, and 3ß-HSD and cell junction proteins, occludin, ß-catenin, and connexin 43; however, none were changed after 6:2 Cl-PFAES exposure. Except for a decrease in the relative epididymis and testis weights in the 1.0 mg/kg/d group, 6:2 Cl-PFAES exposure for 56 d exerted no significant effect on the serum levels of reproductive hormones or the testicular mRNA profilesin adult male mice, implying a relative weak reproductive injury potential compared with that of PFOS.

Solubility Constraints on Aquatic Ecotoxicity Testing of Anionic Surfactants.

In order to develop models that can predict the environmental behavior and effects of chemicals, reliable experimental data are needed. However, for anionic surfactants the number of ecotoxicity studies is still limited. The present study therefore aimed to determine the aquatic ecotoxicity of three classes of anionic surfactants. To this purpose we subjected daphnids (Daphnia magna) for 48 h to alkyl carboxylates (CxCO2-), alkyl sulfonates (CxSO3-), and alkyl sulfates (CxSO4-) with different carbon chain lengths (x). However, all surfactants with x > 11 showed less than 50% immobility at water solubility. Hence, EC50 values for only few surfactants could be gathered: C9CO2- (16 mg L-1), C11CO2- (0.8 mg L-1) and C11SO4- (13.5 mg L-1). Data from these compounds showed an increase in ecotoxicity with a factor 4.5 per addition of a hydrocarbon unit to the alkyl chain, and a factor 20 when replacing the sulfate head group by a carboxylate head group. Unfortunately, we could not test carboxylates with a broader variety of chain lengths because solubility limited the range of chain length that can be tested.

6:2 Chlorinated polyfluorinated ether sulfonate, a PFOS alternative, induces embryotoxicity and disrupts cardiac development in zebrafish embryos.

As an alternative to perfluorooctanesulfonate (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (commercial name: F-53B) has been used as a mist suppressant in Chinese electroplating industries for over 30 years. It has been found in the environment and fish, and one acute assay indicated F-53B was moderately toxic. However, the toxicological information on this compound was incomplete and insufficient for assessment of their environment impact. The object of this study was to examine the developmental toxicity of F-53B using zebrafish embryos. Zebrafish embryos were incubated in 6-well plates with various concentrations of F-53B (1.5, 3, 6, and 12mg/L) from 6 to 132h post fertilization (hpf). Results showed that F-53B exposure induced developmental toxicity, including delayed hatching, increased occurrence of malformations, and reduced survival. Malformations, including pericardial and yolk sac edemas, abnormal spines, bent tails, and uninflated swim bladders, appeared at 84 hpf, and increased with time course and dose. A decrease in survival percentages was noted in the 6 and 12mg/L F-53B-treated groups at 132 hpf. Continuous exposure to 3mg/L F-53B resulted in high accumulation levels in zebrafish embryos, suggesting an inability for embryos to eliminate this compound and a high cumulative risk to fish. We also examined the cardiac function of embryos at specific developmental stages following exposure to different concentrations, and found that F-53B induced cardiac toxicity and reduced heart rate. Even under low F-53B concentration, o-dianisidine staining results showed significant decrease of relative erythrocyte number at 72 hpf before the appearance of observed effects of F-53B on the heart. To elucidate the underlying molecular changes, genes involved in normal cardiac development were analyzed using real-time qPCR in the whole-body of zebrafish embryos. F-53B inhibited the mRNA expression of ß-catenin (ctnnb2) and wnt3a. The mRNA levels of ß-catenin targeted genes (nkx2.5 and sox9b), which play critical roles in cardiogenesis, were also reduced after exposure. Thus, exposure to F-53B impaired the development of zebrafish embryos and disrupted cardiac development, which might be mediated by effects on the Wnt signaling pathway and decrease of erythrocyte numbers.

Occurrence and distribution of perfluoroalkyl acids (PFAAs) in surface water and sediment of a tropical coastal area (Bay of Bengal coast, Bangladesh).

This study reports the first evidence of perfluoroalkyl acids (PFAAs) in surface waters and sediments collected from the coastal area of Bangladesh. Fifteen target PFAAs, including C4-14-PFCAs (perfluoroalkyl carboxylates) and C4, C6, C8, and C10-PFSAs (perfluoroalkyl sulfonates), were quantified by HPLC-MS/MS. The ΣPFAAs in surface water and sediment samples were in the range of 10.6 to 46.8ng/L and 1.07 to 8.15ng/gdw, respectively. PFOA in water (3.17-27.8ng/L) and PFOS in sediment samples (0.60-1.14ng/gdw) were found to be the most abundant PFAAs, and these concentrations were comparable to or less than most other reported values, particularly those recorded from the coastal areas of China, Japan, Korea and Spain. The majority of the monitored PFAAs did not show clear seasonal variation. The southeastern part (Cox's Bazar and Chittagong) of the Bangladeshi coastal area was more contaminated with PFAAs than the southern (Meghna Estuary) and southwestern parts (Sundarbans). Industrial and municipal wastewater effluents, ship breaking and port activities were identified as potential sources of the PFAA contamination in this region. Field-based sediment water distribution coefficients (KD) were calculated and corrected for organic carbon content (KOC), which reduced the variability between samples. The values of log KD (1.63-2.88) and log KOC (4.02-5.16) were higher than previously reported values, which may indicate that the partitioning of PFAAs in a tropical coastal ecosystem is different from other ecosystems, such as temperate and sub-tropical regions. Although a preliminary environmental hazard assessment indicated that PFOA or PFOS levels do not currently exceed the acute safety thresholds, we should keep in mind that they are bioavailable and can accumulate in the food chain. Therefore, the ubiquity of PFAAs in the coastal area of Bangladesh warrants further studies characterizing their specific sources and the potential long-term risks they present to both humans and wildlife.

Aquatic hazard, bioaccumulation and screening risk assessment for 6:2 fluorotelomer sulfonate.

This study assessed the aquatic toxicity and bioaccumulation potential of 6:2 fluorotelomer sulfonate (6:2 FTSA). Acute and chronic aquatic hazard endpoints indicate 6:2 FTSA is not classified for aquatic hazard according to GHS or European CLP legislation. The aqueous bioconcentration factors for 6:2 FTSA were <40 and the dietary assimilation efficiency, growth corrected half-life and dietary biomagnification factor (BMF) were 0.435, 23.1d and 0.295, respectively. These data indicate that 6:2 FTSA is not bioaccumulative in aquatic organisms. Comparison of PNECs with the reported surface water concentrations (non-spill situations) suggests low risk to aquatic organisms from 6:2 FTSA. Future studies are needed to elucidate the biotic and abiotic fate of commercial AFFF surfactants in the environment.

In vitro analysis of the effect of alkyl-chain length of anionic surfactants on the skin by using a reconstructed human epidermal model.

We investigated the effect of the alkyl-chain length of anionic surfactants on the skin using an in vitro model. The evaluated anionic surfactants were sodium alkyl sulfate (AS) and sodium fatty acid methyl ester sulfonate (MES), which had different alkyl-chain lengths (C8-C14). Skin tissue damage and permeability were examined using a reconstructed human epidermal model, LabCyte EPI-MODEL24. Skin tissue damage was examined by measuring cytotoxicity with an MTT assay. Liquid chromatography/tandem mass spectrometry (LC/MS-MS) and liquid chromatography/mass spectrometry (LC/MS) were used to detect surfactants that permeated into the assay medium through an epidermal model. To assess the permeation mechanism and cell damage caused by the surfactants through the epidermis, we evaluated the structural changes of Bovine Serum Albumin (BSA), used as a simple model protein, and the fluidity of 1,2-dipalmitoyl-sn-glycero-3-phosphpcholine (DPPC) liposome, which serves as one of the most abundant phospholipid models of living cell membranes in the epidermis. The effects of the surfactants on the proteins were measured using Circular Dichroism (CD) spectroscopy, while the effects on membrane fluidity were investigated by electron spin resonance (ESR) spectroscopy. ET50 (the 50% median effective time) increased as follows: C10 < C12 < C8 < C14 in AS and C8, C10 < C12 < C14 in MES. The order of permeation through the LabCyte EPI-MODEL24 was C10 > C12 > C14, for both AS and MES. For both AS and MES, the order parameter, which is the criteria for the microscopic viscosity of lipid bilayers, increased as follows: C10 < C12 < C14, which means the membrane fluidity is C10 > C12 > C14. It was determined that the difference in skin tissue damage in the LabCyte EPI-MODEL24 with C10 to C14 AS and MES was caused by the difference in permeation and cell membrane fluidity through the lipid bilayer path in the epidermis.

Structure-activity relationships for perfluoroalkane-induced in vitro interference with rat liver mitochondrial respiration.

Perfluorinated alkyl acids (PFAAs) represent a broad class of commercial products designed primarily for the coatings industry. However, detection of residues globally in a variety of species led to the discontinuation of production in the U.S. Although PFAAs cause activation of the PPARα and CAR nuclear receptors, interference with mitochondrial bioenergetics has been implicated as an alternative mechanism of cytotoxicity. Although the mechanisms by which the eight carbon chain PFAAs interfere with mitochondrial bioenergetics are fairly well described, the activities of the more highly substituted or shorter chain PFAAs are far less well characterized. The current investigation was designed to explore structure-activity relationships by which PFAAs interfere with mitochondrial respiration in vitro. Freshly isolated rat liver mitochondria were incubated with one of 16 different PFAAs, including perfluorinated carboxylic, acetic, and sulfonic acids, sulfonamides and sulfamido acetates, and alcohols. The effect on mitochondrial respiration was measured at five concentrations and dose-response curves were generated to describe the effects on state 3 and 4 respiration and respiratory control. With the exception of PFOS, all PFAAs at sufficiently high concentrations (>20µM) stimulated state 4 and inhibited state 3 respiration. Stimulation of state 4 respiration was most pronounced for the carboxylic acids and the sulfonamides, which supports prior evidence that the perfluorinated carboxylic and acetic acids induce the mitochondrial permeability transition, whereas the sulfonamides are protonophoric uncouplers of oxidative phosphorylation. In both cases, potency increased with increasing carbon number, with a prominent inflection point between the six and eight carbon congeners. The results provide a foundation for classifying PFAAs according to specific modes of mitochondrial activity and, in combination with toxicokinetic considerations, establishing structure-activity-based boundaries for initial estimates of risk for noncancer endpoints for PFAAs for which minimal in vivo toxicity testing currently exists.