As an alternative to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer acid (HFPO-TA) has been increasingly used for fluoropolymer manufacture in recent years. Its growing detection in ...environmental matrices and wildlife raises considerable concern about its potential health risks. Here we investigated the effects of HFPO-TA on mouse liver following 28 days of exposure to 0.02, 0.1, or 0.5 mg/kg/d of HFPO-TA via oral gavage. Results showed that HFPO-TA concentrations increased to 1.14, 4.48, and 30.8 μg/mL in serum and 12.0, 32.2, and 100 μg/g in liver, respectively. Liver injury, including hepatomegaly, necrosis, and increase in alanine aminotransferase activity, was observed. Furthermore, total cholesterol and triglycerides decreased in the liver in a dose-dependent manner. Liver transcriptome analysis revealed that 281, 1001, and 2491 genes were differentially expressed (fold change ≥2 and FDR < 0.05) in the three treated groups, respectively, compared with the control group. KEGG enrichment analysis highlighted the PPAR and chemical carcinogenesis pathways in all three treatment groups. Protein levels of genes involved in carcinogenesis, such as AFP, p21, Sirt1 C-MYC, and PCNA, were significantly increased. Compared with previously published toxicological data of PFOA, HFPO-TA showed higher bioaccumulation potential and more serious hepatotoxicity. Taken together, HFPO-TA does not appear to be a safer alternative to PFOA.
Research on perfluoroalkyl substances (PFASs) continues to grow. However, very little is known about these substances in amphibians. Here we report for the first time on the occurrence, tissue ...distribution, and bioaccumulation of two novel PFASs, chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA) and hexafluoropropylene oxide trimer acid (HFPO-TA), in the black-spotted frog (Pelophylax nigromaculatus) from China. Frogs from cities with large-scale fluorochemical industries had significantly greater liver ∑PFAS levels (mean 54.28 ng/g in Changshu; 31.22 ng/g in Huantai) than those from cities without similar industry (9.91 ng/g in Zhoushan; 7.68 ng/g in Quzhou). Females had significantly lower liver PFAS levels than males, and older frogs tended to have lower PFAS levels than younger frogs. Skin, liver, and muscle contributed nearly 80% to the whole body burden of 6:2 Cl-PFESA in males, whereas the female ovary alone accounted for 58.4%. These results suggest substantial maternal transfer of 6:2 Cl-PFESA to eggs, raising concern regarding its developmental toxicity on frogs and other species. The bioaccumulation factor results (6:2 Cl-PFESA > PFOS; HFPO-TA > PFOA) suggest a stronger accumulative potential in the black-spotted frog for these alternative substances compared to their predecessors. Future studies on their toxicity and ecology risk are warranted.
Driven by increasingly stringent restrictions on long-chain per- and polyfluoroalkyl substances (PFASs), novel fluorinated compounds have emerged on the market. Here we report on the occurrences of ...several perfluoroalkyl ether carboxylic and sulfonic acids (PFECAs and PFESAs), including hexafluoropropylene oxide dimer and trimer acids (HFPO-DA and HFPO-TA), ammonium 4,8-dioxa-3H-perfluorononanoate (ADONA), chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA), and its hydrogen-substituted analogue (6:2 H-PFESA) in surface waters from China (n = 106), the United States (n = 12), the United Kingdom (n = 6), Sweden (n = 10), Germany (n = 14), The Netherlands (n = 6), and Korea (n = 6). Results showed that HFPO-DA, HFPO-TA, and 6:2 Cl-PFESA (median = 0.95, 0.21, and 0.31 ng/L, respectively) were frequently detected in all countries, indicating ubiquitous dispersal and distribution in global surface waters. The presence of 6:2 H-PFESA was widely detected in China (detection rate > 95%) but not in any other country. Only trace levels of ADONA (0.013–1.5 ng/L) were detected in the Rhine River flowing through Germany. The estimated total riverine mass discharges of HFPO-DA, HFPO-TA, and ΣPFESAs reached 2.6, 6.0, and 4.3 ton/year in five of the major river systems in China. Our results indicated that novel PFECAs and PFESAs might become global contaminants, and future investigations are warranted.
•F–53B caused delayed hatching, increased the occurrence of malformations, and reduced survival.•Exposure to 3mg/L F–53B resulted in high accumulation of the compound in zebrafish embryos.•F–53B ...induced cardiac toxicity and reduced heart rate.•F–53B might affect Wnt signaling pathway and decrease the erythrocyte numbers.
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 β-catenin (ctnnb2) and wnt3a. The mRNA levels of β-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.
Here, we report on the occurrence of a novel perfluoroalkyl ether carboxylic acid, ammonium perfluoro-2-(propoxy)propoxy-1-propanoate (HFPO-TA), in surface water and common carp (Cyprinus carpio) ...collected from the Xiaoqing River and in residents residing near a fluoropolymer production plant in Huantai County, China. Compared with the levels upstream of the Xiaoqing River, HFPO-TA concentrations (5200–68500 ng/L) were approximately 120–1600-times higher downstream after receiving fluoropolymer plant effluent from a tributary. The riverine discharge of HFPO-TA was estimated to be 4.6 t/yr, accounting for 22% of total PFAS discharge. In the wild common carp collected downstream from the point source, HFPO-TA was detected in the blood (median: 1510 ng/mL), liver (587 ng/g ww), and muscle (118 ng/g ww). The log BCFblood of HFPO-TA (2.18) was significantly higher than that of PFOA (1.93). Detectable levels of HFPO-TA were also found in the sera of residents (median: 2.93 ng/mL). This is the first report on the environmental occurrence and bioaccumulation of this novel chemical. Our results indicate an emerging usage of HFPO-TA in the fluoropolymer manufacturing industry and raise concerns about the toxicity and potential health risks of HFPO-TA to aquatic organisms and humans.
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.
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•Bioconcentration of F-53B was gender-dependent, and transfer from parent to eggs.•Similar to PFOS, F-53B exposure inhibited the growth and reproduction of zebrafish.•F-53B exposure altered sex hormone level and expression of genes along HPGL axis.•Transcriptome analysis showed F-53B exposure disrupted spermatogenesis in male fish.•Parental exposure to F-53B could impair embryonic development of offspring.
Long-term exposure to F-53B for one generation had adverse effects on reproduction in both F0 and F1 adult fish and impaired embryonic development of offspring.
•Nationwide distribution of PFECA was observed in Chinese diets.•HFPO-DA was identified as the dominant compound in diet.•Cereals are the primary contributors to PFECA intake.•EDI of HFPO-DA ranges ...from 0.78 to 1.32 times the EPA RfD.
With the phase-out of perfluorooctanoic acid (PFOA) and its replacement by perfluoroalkyl ether carboxylic acids (PFECAs), there is a potential for increased exposure to various new PFECAs among the general population in China. While there are existing studies on dietary exposure to legacy perfluoroalkyl and polyfluoroalkyl substances (PFASs), research on dietary exposure to PFECAs, especially among the general Chinese populace, remains scarce. In the present study, we investigated the distribution of PFECAs in dietary sources from 33 cities across five major regions in China, along with the associated dietary intake. Analysis indicated that aquatic animal samples contained higher concentrations of legacy PFASs compared to those from terrestrial animals and plants. In contrast, PFECAs were found in higher concentrations in plant and terrestrial animal samples. Notably, hexafluoropropylene oxide dimer (HFPO-DA) was identified as the dominant compound in vegetables, cereals, pork, and mutton across the five regions, suggesting widespread dietary exposure. PFECAs constituted the majority of PFAS intake (57 %), with the estimated daily intake (EDI) of HFPO-DA ranging from 2.33 to 3.96 ng/kg bw/day, which corresponds to 0.78–1.32 times the reference dose (RfD) (3.0 ng/kg bw/day) set by the United States Environmental Protection Agency. Given the ubiquity of HFPO-DA and many other PFECAs in the nationwide diet of China, there is an urgent need for further research into these chemicals to establish relevant safety benchmarks or consumption advisory values for the diet.
•Associations between 11 PFASs and 5 steroids in cord sera were assessed.•F-53B, as Chinese unique PFOS replacement, was associated with cortisol in girls.•PFBS, PFOS and PFHxS were positively ...associated with progesterone in newborns.•Seven PFASs were positively associated with 11-deoxycortisol, the precursor of cortisol.•The results indicate that PFOS and its replacements may influence neonatal steroids.
Exposure to per-/polyfluoroalkyl substances (PFASs) can disrupt endocrine hormones in humans. Prior studies have focused on the harmful effects of the two traditional per-/polyfluoroalkyl substances (PFASs), perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Other PFASs, used as the replacements of PFOS and PFOA, are widely and increasingly detected in humans. Whether these replacements influence glucocorticoids and progestogens in newborns remains unknown.
To investigate the associations between exposures of PFOS, PFOA and their replacements and glucocorticoids and progestogens in newborns.
We measured the concentrations of 13 PFASs, 3 glucocorticoids (11-deoxycortisol, cortisol and cortisone) and 2 progestogens progesterone, 17-hydroxyprogesterone (17OHP) in the cord sera of 374 neonates in a birth cohort from Wuhan, China, between 2013 and 2014. We evaluated the associations of each PFAS with glucocorticoids and progestogens using multiple linear regression models, and multiple comparisons were additionally corrected via false discovery rates (FDR).
Out of the 13 PFASs, 9 were detected in over 95% of cord sera. The Chinese specific PFOS replacement − 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA, trade name F-53B) was positively associated with 13.13% change in cortisol in girls (95% CI = 4.47%, 22.52%, for each IQR increase in 6:2 Cl-PFESA). Seven PFASs had positive associations with the precursor of cortisol, namely 11-deoxycortisol (percent change ranged from 6.41% to 11.24%, for each IQR increase in PFASs). Perfluorobutane sulfonate (PFBS) in cord sera was positively associated with progesterone in the linear model, whereas PFOS and perfluorohexane sulfonate (PFHxS) levels were associated with progesterone in the quartile models. No PFASs were related to 17OHP or cortisone.
In this study, PFOS, PFOA and/or their replacements were positively associated with progesterone, cortisol and 11-deoxycortisol in newborns. These results suggested that not only PFOS and PFOA, but also other PFASs have potential impacts on glucocorticoids and progestogens in newborns.
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•A soft body detonation driver can be used to design a novel and efficient frog-like jumping robot.•The detonation reaction of the hydrogen–oxygen gas mixed in the soft body cavity is ...controlled to simulate the explosive force of the frog’s hindlimbs during jumping.•Controlling the motion state of the forelimb mechanism to simulate the change of the starting posture angle of the frog in jumping.•Our frog-like jumping robot with a soft-body detonation drive has a jumping dynamic similarity with frogs.
Inspired by the instantaneous power of the hindlimbs of frogs and the dexterous posture adjustment of their forelimbs, a frog-like jumping robot based on a soft body detonation drive was designed. By combining the flexibility of silicone material and the detonation characteristics of mixed hydrogen–oxygen gas, a soft body detonation driver was constructed to cause the robot to jump from the hindlimbs to achieve a high energy instantaneous explosive force. Moreover, a spring-based forelimb mechanism is designed. This mechanism not only adjusts the robot with different starting jump posture angles but also maintains a smooth landing by providing cushioning. The kinematics and efficiency models of jumping are also established by the D-H parameter method and geometric method, and they are verified and analysed. Finally, combined with the control system, an experimental prototype (weight 495 g) with a height of 135 mm, a trunk length of 120 mm, front and hindlimbs of 195 mm, and a width of 90 mm is developed. The experiment proved that the robot can not only achieve 6 consecutive jumps, a single jump height of 0.6 m and a spanning distance of 1.2 m but also easily cross rectangular obstacles.
•Urinary MBP and MiBP in Chinese men were higher than the values in other countries.•Serum levels of INSL3 was negatively associated with MEHP and %MEHP in urine.•Acrosin activity was negatively ...associated with MBP, MiBP, MEHP and %MEHP.•Serum levels of T and LH were negatively associated with MBP and MiBP simultaneously.
Phthalates are suspected endocrine disrupting chemicals that impair male reproductive function in animal and epidemiological studies. We investigated associations between urinary phthalate metabolites and acrosin activity, along with that between insulin like-factor 3 (INSL3), a Leydig cell function marker, in Chinese adult men and assessed the association between the metabolites and male reproductive function. Serum levels of INSL3 and other hormones, semen parameters, and urinary concentrations of 14 phthalate metabolites in 1066 men were measured. The unadjusted concentrations of phthalates were included as independent variables and urinary creatinine as a separate covariate. INSL3 was negatively associated with mono-2-ethylhexyl phthalate (MEHP) and %MEHP percentage of MEHP to all di(2-ethylhexyl) phthalate (DEHP) metabolites. Acrosin activity was negatively associated with mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), MEHP and %MEHP. MBP and MiBP were also negatively associated with total testosterone (T), free androgen index (FAI), free testosterone (FT), luteinizing hormone (LH) and sperm morphology and positively associated with DNA fragmentation index (DFI). A negative association between %MEHP and sperm motility was observed. Several other metabolites were also associated with reproductive function. This is the first report on the inverse associations of phthalate metabolites with acrosin activity and INSL3. Phthalates may cause multiple adverse results on reproductive function at environmental levels.
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