Here, we review present understanding of sources and trends in human exposure to poly- and perfluoroalkyl substances (PFASs) and epidemiologic evidence for impacts on cancer, immune function, ...metabolic outcomes, and neurodevelopment. More than 4000 PFASs have been manufactured by humans and hundreds have been detected in environmental samples. Direct exposures due to use in products can be quickly phased out by shifts in chemical production but exposures driven by PFAS accumulation in the ocean and marine food chains and contamination of groundwater persist over long timescales. Serum concentrations of legacy PFASs in humans are declining globally but total exposures to newer PFASs and precursor compounds have not been well characterized. Human exposures to legacy PFASs from seafood and drinking water are stable or increasing in many regions, suggesting observed declines reflect phase-outs in legacy PFAS use in consumer products. Many regions globally are continuing to discover PFAS contaminated sites from aqueous film forming foam (AFFF) use, particularly next to airports and military bases. Exposures from food packaging and indoor environments are uncertain due to a rapidly changing chemical landscape where legacy PFASs have been replaced by diverse precursors and custom molecules that are difficult to detect. Multiple studies find significant associations between PFAS exposure and adverse immune outcomes in children. Dyslipidemia is the strongest metabolic outcome associated with PFAS exposure. Evidence for cancer is limited to manufacturing locations with extremely high exposures and insufficient data are available to characterize impacts of PFAS exposures on neurodevelopment. Preliminary evidence suggests significant health effects associated with exposures to emerging PFASs. Lessons learned from legacy PFASs indicate that limited data should not be used as a justification to delay risk mitigation actions for replacement PFASs.
The spatial distribution of 29 per- and polyfluoroalkyl substances (PFASs) in seawater was investigated along a sampling transect from Europe to the Arctic and two transects within Fram Strait, ...located between Greenland and Svalbard, in the summer of 2018. Hexafluoropropylene oxide-dimer acid (HFPO-DA), a replacement compound for perfluorooctanoic acid (PFOA), was detected in Arctic seawater for the first time. This provides evidence for its long-range transport to remote areas. The total PFAS concentration was significantly enriched in the cold, low-salinity surface water exiting the Arctic compared to warmer, higher-salinity water from the North Atlantic entering the Arctic (260 ± 20 pg/L versus 190 ± 10 pg/L). The higher ratio of perfluoroheptanoic acid (PFHpA) to perfluorononanoic acid (PFNA) in outflowing water from the Arctic suggests a higher contribution of atmospheric sources compared to ocean circulation. An east–west cross section of the Fram Strait, which included seven depth profiles, revealed higher PFAS concentrations in the surface water layer than in intermediate waters and a negligible intrusion into deep waters (>1000 m). Mass transport estimates indicated a net inflow of PFASs with ≥8 perfluorinated carbons via the boundary currents and a net outflow of shorter-chain homologues. We hypothesize that this reflects higher contributions from atmospheric sources to the Arctic outflow and a higher retention of the long-chain compounds in melting snow and ice.
This commentary presents a scientific basis for managing as one chemical class the thousands of chemicals known as PFAS (per- and polyfluoroalkyl substances). The class includes perfluoroalkyl acids, ...perfluoroalkylether acids, and their precursors; fluoropolymers and perfluoropolyethers; and other PFAS. The basis for the class approach is presented in relation to their physicochemical, environmental, and toxicological properties. Specifically, the high persistence, accumulation potential, and/or hazards (known and potential) of PFAS studied to date warrant treating all PFAS as a single class. Examples are provided of how some PFAS are being regulated and how some businesses are avoiding all PFAS in their products and purchasing decisions. We conclude with options for how governments and industry can apply the class-based approach, emphasizing the importance of eliminating non-essential uses of PFAS, and further developing safer alternatives and methods to remove existing PFAS from the environment.
Oceans have remained the least well-researched reservoirs of persistent organic pollutants (POPs) globally, due to their vast scale, difficulty of access, and challenging (trace) analysis. Little ...data on POPs exists along South America and the effect of different currents and river plumes on aqueous concentrations. Research cruise KN210-04 (R/V Knorr) offered a unique opportunity to determine POP gradients in air, water, and their air–water exchange along South America, covering both hemispheres. Compounds of interest included polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenylethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs). Remote tropical Atlantic Ocean atmospheric concentrations varied little between both hemispheres; for HCB, BDEs 47 and 99, they were ∼5 pg/m3, PCBs were ∼1 pg/m3, α-HCH was ∼0.2 pg/m3, and phenanthrene and other PAHs were in the low 100s pg/m3. Aqueous concentrations were dominated by PCB 52 (mean 4.1 pg/L), HCB (1.6 pg/L), and β-HCH (1.9 pg/L), with other compounds <1 pg/L. Target PCBs tended to undergo net volatilization from the surface ocean, while gradients indicated net deposition for a-HCH. In contrast to atmospheric concentrations, which were basically unchanged between hemispheres, we detected strong gradients in aqueous POPs, with mostly nondetects in the tropical western South Atlantic. These results highlight the importance of currents and loss processes on ocean scales for the distribution of POPs.
The protease renin is the key enzyme of the renin-angiotensin-aldosterone cascade, which is relevant under both physiological and pathophysiological settings. The kidney is the only organ capable of ...releasing enzymatically active renin. Although the characteristic juxtaglomerular position is the best known site of renin generation, renin-producing cells in the kidney can vary in number and localization. (Pro)renin gene transcription in these cells is controlled by a number of transcription factors, among which CREB is the best characterized. Pro-renin is stored in vesicles, activated to renin, and then released upon demand. The release of renin is under the control of the cAMP (stimulatory) and Ca(2+) (inhibitory) signaling pathways. Meanwhile, a great number of intrarenally generated or systemically acting factors have been identified that control the renin secretion directly at the level of renin-producing cells, by activating either of the signaling pathways mentioned above. The broad spectrum of biological actions of (pro)renin is mediated by receptors for (pro)renin, angiotensin II and angiotensin-(1-7).
The kidneys are an important target for angiotensin II (ANG II). In adult kidneys, the effects of ANG II are mediated mainly by ANG II type 1 (AT
) receptors. AT
receptor expression has been reported ...for a variety of different cell types within the kidneys, suggesting a broad spectrum of actions for ANG II. Since there have been heterogeneous results in the literature regarding the intrarenal distribution of AT
receptors, this study aimed to obtain a comprehensive overview about the localization of AT
receptor expression in mouse, rat, and human kidneys. Using the cell-specific and high-resolution RNAscope technique, we performed colocalization experiments with various cell markers to specifically discriminate between different segments of the tubular and vascular system. Overall, we found a similar pattern of AT
mRNA expression in mouse, rat, and human kidneys. AT
receptors were detected in mesangial cells and renin-producing cells. In addition, AT
mRNA was found in interstitial cells of the cortex and outer medulla. In rodents, late afferent and early efferent arterioles expressed AT
receptor mRNA, but larger vessels of the investigated species showed no AT
expression. Tubular expression of AT
mRNA was species dependent with a strong expression in proximal tubules of mice, whereas expression was undetectable in human tubular cells. These findings suggest that the (juxta)glomerular area and tubulointerstitium are conserved expression sites for AT
receptors across species and might present the main target sites for ANG II in adult human and rodent kidneys.
Angiotensin II (ANG II) type 1 (AT
) receptors are essential for mediating the effects of ANG II in the kidneys. This study aimed to obtain a comprehensive overview about the cell-specific localization of AT
receptor expression in rodent and human kidneys using the novel RNAscope technique. We found that the conserved AT
receptor mRNA expression sites across species are the (juxta)glomerular areas and tubulointerstitium, which might present main target sites for ANG II in adult human and rodent kidneys.
Food contact materials (FCMs) are intended to be in contact with food during production, handling or storage. They are one possible source of food contamination, because chemicals may migrate from ...the material into the food. More than 6000 FCM substances appear on regulatory or non-regulatory lists. Some of these substances have been linked to chronic diseases, whilst many others lack (sufficient) toxicological evaluation. The aim of this study was the identification of known FCM substances that are also considered to be chemicals of concern (COCs). The investigation was based on the following three FCM lists: (1) the 2013 Pew Charitable Trusts database of direct and indirect food additives legally used in the United States (or Pew for short), (2) the current European Union-wide positive list for plastic FCMs (or Union for short), and (3) the 2011 non-plastics FCM substances database published by EFSA (or ESCO for short). These three lists of food contact substances (Pew, Union, ESCO lists) were compared with the Substitute It Now! (SIN) list 2.1, which includes chemicals fulfilling the criteria listed in article 57 of Regulation (EC) No. 1907/2006 (REACH), and the TEDX database on endocrine-disrupting chemicals. A total of 175 chemicals used in FCMs were identified as COCs. Fifty-four substances present on the SIN list 2.1 were also found on the Union and/or ESCO lists. Twenty-one of those 54 substances are candidates for Substances of Very High Concern (SVHC), and six of these 21 are listed on Annex XIV and intended for phase-out under REACH. In conclusion, COCs used in FCMs were identified and information about their applications, regulatory status and potential hazards was included.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Human activities have released large quantities of neutral persistent organic pollutants (POPs) that may be biomagnified in food webs and pose health risks to wildlife, particularly top predators. ...Here we develop a global 3‐D ocean simulation for four polychlorinated biphenyls (PCBs) spanning a range of molecular weights and volatilities to better understand effects of climate‐driven changes in ocean biogeochemistry on the lifetime and distribution of POPs. Observations are most abundant in the Arctic Ocean. There, model results reproduce spatial patterns and magnitudes of measured PCB concentrations. Sorption of PCBs to suspended particles and subsequent burial in benthic marine sediment is the dominant oceanic loss process globally. Results suggest benthic sediment burial has removed 75% of cumulative PCB releases since the onset of production in 1930. Wind speed, light penetration, and ocean circulation exert a stronger and more variable influence on volatile PCB congeners with lower particle affinity such as chlorinated biphenyl‐28 and chlorinated biphenyl‐101. In the Arctic Ocean between 1992 and 2015, modeled evasion (losses) of the more volatile PCB congeners from the surface ocean increased due to declines in sea ice and changes in ocean circulation. By contrast, net deposition increased slightly for higher molecular weight congeners with stronger partitioning to particles. Our results suggest future climate changes will have the greatest impacts on the chemical lifetimes and distributions of volatile POPs with lower molecular weights.
Key Points
Climate change will have the greatest impacts on the chemical lifetimes and distributions of volatile persistent organic pollutants
Marine sediment has sequestered 75% of cumulative releases of polychlorinated biphenyls since the onset of production in 1930
Arctic sea ice retreat is likely to enhance losses of volatile congeners but increase net deposition of higher molecular weight congeners
The Arctic Ocean is known to be contaminated by various persistent organic pollutants (POPs). The Fram Strait, the only deepwater passage to the Arctic Ocean (from the Atlantic Ocean), represents an ...unquantified gateway for POPs fluxes into and out of the Arctic. Polyethylene passive samplers were deployed in vertical profiles in the Fram Strait and in air and surface water in the Canadian Archipelago to determine the concentrations, profiles, and mass fluxes of dissolved polychlorinated biphenyls (PCBs) and organochlorine pesticides. In the Fram Strait, higher concentrations of ΣPCBs (1.3–3.6 pg/L) and dichlorodiphenyltrichloroethanes (ΣDDTs, 5.2–9.1 pg/L) were observed in the deepwater masses (below 1,000 m), similar to nutrient‐like vertical profiles. There was net southward transport of hexachlorobenzene and hexachlorocyclohexanes (ΣHCHs) of 0.70 and 14 Mg/year but a net northward transport of ΣPCBs at 0.16 Mg/year through the Fram Strait.
Plain Language Summary
Persistent organic pollutants can reach the Arctic Ocean by long‐range atmospheric transport, ocean currents, and inputs from the large Arctic rivers. Polychlorinated biphenyls (PCBs) and organochlorine pesticides, which have been extensively used since the 1930s, were banned and listed in the United Nations Environment Programme Stockholm Convention on persistent organic pollutants in 2001. We performed the first pan‐Arctic deployments of passive samplers to gain knowledge of the occurrence, transport, and fate of these legacy contaminants in the remote Arctic. Our results demonstrated the ubiquitous presence of persistent industrial and agricultural contaminants across the Canadian Arctic and throughout the water column of the Fram Strait. While atmospheric transport seems mostly responsible for the presence of these pollutants in the surface Arctic Ocean, in the Fram Strait, concentrations of PCBs and dichlorodiphenyltrichloroethanes (DDTs) increased in deep waters, indicating their penetration to the deep ocean environment. Our results also showed the legacy hexachlorocyclohexanes (HCHs) and hexachlorobenzene (HCB) are released from the Arctic Ocean to the Atlantic Ocean via the deepwater Fram Strait, while PCBs are still loaded from the Atlantic Ocean to the Arctic Ocean.
Key Points
Deep waters of the Fram Strait carried highest concentrations of polychlorinated biphenyls and dichlorodiphenyltrichloroethane
A fractionation of organic pollutants with depth was observed; contributions of the more hydrophobic compounds increased with depth
There is a net export of hexachlorocyclohexanes and hexachlorobenzene from the Arctic Ocean through the deepwater passage Fram Strait
Sixteen cycles of Brentuximab vedotin (BV) after autologous stem cell transplant (ASCT) in high-risk relapsed/refractory classical Hodgkin lymphoma demonstrated an improved 2-year progression-free ...survival (PFS) over placebo. However, most patients are unable to complete all 16 cycles at full dose due to toxicity. This retrospective, multicenter study investigated the effect of cumulative maintenance BV dose on 2-year PFS. Data were collected from patients who received at least one cycle of BV maintenance after ASCT with one of the following high-risk features: primary refractory disease (PRD), extra-nodal disease (END), or relapse <12 months (RL<12) from the end of frontline therapy. Cohort 1 had patients with >75% of the planned total cumulative dose, cohort 2 with 51-75% of dose, and cohort 3 with ≤50% of dose. The primary outcome was 2-year PFS. A total of 118 patients were included. Fifty percent had PRD, 29% had RL<12, and 39% had END. Forty-four percent of patients had prior exposure to BV and 65% were in complete remission before ASCT. Only 14% of patients received the full planned BV dose. Sixty-one percent of patients discontinued maintenance early and majority of those (72%) were due to toxicity. The 2-year PFS for the entire population was 80.7%. The 2-year PFS was 89.2% for cohort 1 (n=39), 86.2% for cohort 2 (n=33), and 77.9% for cohort 3 (n=46) (P=0.70). These data are reassuring for patients who require dose reductions or discontinuation to manage toxicity.
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