Analysis of perfluorinated compounds in human serum from the general population in Shanghai by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
“…PFOS can cross the blood-brain barrier less efficient than PFOA 72 , but the LOECs reported here for PFOS are lower than for PFOA. Reported plasma or serum concentrations for PFOS fall in the range between 0.002-1.3 µM in the general population [71][72][73] and in occupationally exposed workers the levels are even higher, ranging from 0.27 to 10 µM 70,71 . LOECs on GABA A receptor data and on spike activity in an hiPSC-derived neuronal co-culture reported in this study are www.nature.com/scientificreports www.nature.com/scientificreports/ within or below the range found in human plasma levels.…”
Section: Discussionmentioning
confidence: 99%
“…For PFOS and PFOA human serum to plasma ratios are 1:1 70 . Reported plasma or serum concentrations for PFOA fall for the general population in the range between 0.001-0.2 µM [71][72][73] . In the occupationally exposed population, levels as high as 2.5 µM are found 70 .…”
Concerns about the neurotoxic potential of polyfluoroalkyl substances (PFAS) such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) increase, although their neurotoxic mechanisms of action remain debated. Considering the importance of the GABA A receptor in neuronal function, we investigated acute effects of PFAS on this receptor and on spontaneous neuronal network activity. PFOS (Lowest Observed Effect Concentration (LOEC) 0.1 µM) and PFOA (LOEC 1 µM) inhibited the GABA-evoked current and acted as non-competitive human GABA A receptor antagonists. Network activity of rat primary cortical cultures increased following exposure to PFOS (LOEC 100 µM). However, exposure of networks of human induced pluripotent stem cell (hiPSC)-derived neurons decreased neuronal activity. The higher sensitivity of the α 1 β 2 γ 2L GABA A receptor for PFAS as compared to neuronal networks suggests that PFAS have additional mechanisms of action, or that compensatory mechanisms are at play. Differences between rodent and hiPSC-derived neuronal networks highlight the importance of proper model composition. LOECs for PFAS on GABA A receptor and neuronal activity reported here are within or below the range found in blood levels of occupationally exposed humans. For PFOS, LOECs are even within the range found in human serum and plasma of the general population, suggesting a clear neurotoxic risk. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are well-known perfluoroalkyl substances (PFAS) consisting of an eight-carbon chain in which hydrogen atoms have been substituted with fluorine. Their combined hydrophobic, hydrophilic, oleophobic and lipophobic properties make them ideal industrial surfactants for the manufacturing of consumer products, including paint, stain repellents, fire-fighting foams, and non-stick cookware coatings. The strong carbon-fluorine bond renders PFOS and PFOA highly persistent and studies have shown their presence in the environment, wildlife and even human blood (for reviews see 1,2). By 2002, production of PFOS was phased out and production phase out of PFOA followed in 2006 3. Recent studies indicate that these efforts may be responsible for a reduction in human blood levels in some areas, but the long half-lives of PFOS and PFOA result in slow elimination from environment and humans 4,5. Research has demonstrated that the (developing) nervous system is one of the most sensitive targets for PFOS and PFOA. In mice and rats exposed pre-and/or neonatally to PFOS or PFOA, increased motor activity, decreased habituation and deficits in spatial learning and memory abilities have been observed 6-11. Developmental neurotoxicity has also been observed in other species, including chicken 12 and zebrafish larvae 13,14. However, epidemiological studies have been inconclusive on the risks of PFAS exposure on neurodevelopment. Some studies indicate an association between prenatal PFOS and/or PFOA exposure and an increased risk on congenital cerebral palsy 15 , neuro-behavioural developmen...
“…PFOS can cross the blood-brain barrier less efficient than PFOA 72 , but the LOECs reported here for PFOS are lower than for PFOA. Reported plasma or serum concentrations for PFOS fall in the range between 0.002-1.3 µM in the general population [71][72][73] and in occupationally exposed workers the levels are even higher, ranging from 0.27 to 10 µM 70,71 . LOECs on GABA A receptor data and on spike activity in an hiPSC-derived neuronal co-culture reported in this study are www.nature.com/scientificreports www.nature.com/scientificreports/ within or below the range found in human plasma levels.…”
Section: Discussionmentioning
confidence: 99%
“…For PFOS and PFOA human serum to plasma ratios are 1:1 70 . Reported plasma or serum concentrations for PFOA fall for the general population in the range between 0.001-0.2 µM [71][72][73] . In the occupationally exposed population, levels as high as 2.5 µM are found 70 .…”
Concerns about the neurotoxic potential of polyfluoroalkyl substances (PFAS) such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) increase, although their neurotoxic mechanisms of action remain debated. Considering the importance of the GABA A receptor in neuronal function, we investigated acute effects of PFAS on this receptor and on spontaneous neuronal network activity. PFOS (Lowest Observed Effect Concentration (LOEC) 0.1 µM) and PFOA (LOEC 1 µM) inhibited the GABA-evoked current and acted as non-competitive human GABA A receptor antagonists. Network activity of rat primary cortical cultures increased following exposure to PFOS (LOEC 100 µM). However, exposure of networks of human induced pluripotent stem cell (hiPSC)-derived neurons decreased neuronal activity. The higher sensitivity of the α 1 β 2 γ 2L GABA A receptor for PFAS as compared to neuronal networks suggests that PFAS have additional mechanisms of action, or that compensatory mechanisms are at play. Differences between rodent and hiPSC-derived neuronal networks highlight the importance of proper model composition. LOECs for PFAS on GABA A receptor and neuronal activity reported here are within or below the range found in blood levels of occupationally exposed humans. For PFOS, LOECs are even within the range found in human serum and plasma of the general population, suggesting a clear neurotoxic risk. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are well-known perfluoroalkyl substances (PFAS) consisting of an eight-carbon chain in which hydrogen atoms have been substituted with fluorine. Their combined hydrophobic, hydrophilic, oleophobic and lipophobic properties make them ideal industrial surfactants for the manufacturing of consumer products, including paint, stain repellents, fire-fighting foams, and non-stick cookware coatings. The strong carbon-fluorine bond renders PFOS and PFOA highly persistent and studies have shown their presence in the environment, wildlife and even human blood (for reviews see 1,2). By 2002, production of PFOS was phased out and production phase out of PFOA followed in 2006 3. Recent studies indicate that these efforts may be responsible for a reduction in human blood levels in some areas, but the long half-lives of PFOS and PFOA result in slow elimination from environment and humans 4,5. Research has demonstrated that the (developing) nervous system is one of the most sensitive targets for PFOS and PFOA. In mice and rats exposed pre-and/or neonatally to PFOS or PFOA, increased motor activity, decreased habituation and deficits in spatial learning and memory abilities have been observed 6-11. Developmental neurotoxicity has also been observed in other species, including chicken 12 and zebrafish larvae 13,14. However, epidemiological studies have been inconclusive on the risks of PFAS exposure on neurodevelopment. Some studies indicate an association between prenatal PFOS and/or PFOA exposure and an increased risk on congenital cerebral palsy 15 , neuro-behavioural developmen...
“…Further, a 10-fold increase in PFNA levels in the liver of northern sea otters (Enhydra lutris) was seen from 2004 to 2007 (Hart, Gill, & Kannan, 2009). In a recent study, Wu et al (2017) have reported that PFNA is among one of the second most dominating PFAAs in Shanghai population, with a mean serum concentration of 2.16 ng/mL. PFAAs including PFNA have been shown to cause hepatotoxicity, immunotoxicity and developmental toxicity (Das et al, 2015;Fang, Zhang, Feng, Zhao, & Dai, 2008;Lau et al, 2007;Wang, Yan, Zhang, Zhang, & Dai, 2015).…”
Perfluoroalkyl acids (PFAAs) are widely used in commercial applications and that they are ubiquitous and persistent in the environment. Perfluorononanoic acid (PFNA), a member of PFAAs, has been detected in human and wildlife. Previous acute exposure studies have shown the adverse effect of PFNA on the testis. The present study was aimed to examine the effect of chronic PFNA exposure, from prepuberty to adulthood, on testicular functions and fertility in Parkes (P) male mice and to investigate the possible mechanism(s) of its action. PFNA (0.2 and 0.5 mg/kg) was orally administered to P male mice for 90 days from prepuberty (postnatal day [PND] 25) to adulthood (PND 114). Histologically, testes in PFNA‐treated mice showed non‐uniform degenerative changes in the seminiferous tubules. The treatment also had adverse effects on testicular expression of steroidogenic markers, serum levels of cholesterol and testosterone, sperm parameters and on litter size. A marked increase in the level of lipid peroxidation and decrease in the activities of antioxidant enzymes were observed in the testis of PFNA‐treated mice compared to controls. Further, a significant decrease in expression of proliferating cell nuclear antigen (PCNA) and in the number of PCNA‐positive cells, and an increase in expression of caspase‐3 were also noted in PFNA‐treated mice testis. In conclusion, the results suggest that chronic exposure to PFNA in male mice interferes with testosterone biosynthesis and causes oxidative stress in the testis, leading to alterations in spermatogenesis, sperm quality and fertility potential.
“…PFOA and PFOS are of current concern because of their environmental contamination and human exposure. Millions of people around the world are in the risk of PFOA and PFOS toxicity through drinking water (Hu et al, 2016; Wu et al, 2017; Zeng et al, 2019; Rashid, Ramakrishnan, Fields, & Irudayaraj, 2020). In particular, PFOA is a hepatoxic agent found to impair hepatocyte proliferation, detoxification, and lipid metabolism in the liver.…”
Section: Epigenetic Changes Link Ecs To Adverse Health Outcomesmentioning
Environmental epigenetic findings shed new light on the roles of epigenetic regulations in environmental exposure‐induced toxicities or disease susceptibilities. Currently, environmental emerging contaminants (ECs) are in focus for further investigation due to the evidence of human exposure in addition to their environmental occurrences. However, the adverse effects of these environmental ECs on health through epigenetic mechanisms are still poorly addressed in many aspects. This review discusses the epigenetic mechanisms (DNA methylation, histone modifications, and microRNA expressions) linking ECs exposure to health outcomes. We emphasized on the recent literature describing how ECs can dysregulate epigenetic mechanisms and lead to downstream health outcomes. These up‐to‐date research outputs could provide novel insights into the toxicological mechanisms of ECs. However, the field still faces a demand for further studies on the broad spectrum of health effects, synergistic/antagonistic effects, transgenerational epigenetic effects, and epidemiologic and demographic data of ECs.
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