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Sökning: WFRF:(McLachlan Michael)

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1.
  • Ademuyiwa, Adesoji O., et al. (författare)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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2.
  • Locke, Adam E, et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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4.
  • Lagou, Vasiliki, et al. (författare)
  • Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
  • 2021
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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5.
  • Pennells, Lisa, et al. (författare)
  • Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
  • 2019
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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7.
  • Álvarez-Ruiz, Rodrigo, et al. (författare)
  • Postflood Monitoring in a Subtropical Estuary and Benchmarking with PFASs Allows Measurement of Chemical Persistence on the Scale of Months
  • 2021
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 55:21, s. 14607-14616
  • Tidskriftsartikel (refereegranskat)abstract
    • Measurements of chemical persistence in natural environments can provide insight into behavior not easily replicated in laboratory studies. However, it is difficult to find environmental situations suitable for such measurements, particularly for substances with half-lives exceeding several weeks. The objective of this study was to demonstrate that a strategic postflood monitoring campaign can be used to quantify transformation half-lives on the scale of months in a real aquatic system. Water samples were collected in the upper Brisbane River estuary on 36 occasions over 37 weeks and analyzed for 127 pharmaceuticals and personal care products (PPCPs), pesticides, and perfluoroalkyl substances (PFASs). High quality time trend data were obtained for 41 substances. For many of these, data on the input of a wastewater treatment plant to the upper estuary were also obtained. A mass balance model of the estuary stretch was formulated and parametrized using PFASs as persistent benchmarking chemicals. Transformation half-life estimates were obtained for 10 PPCPs and 7 pesticides ranging from 18 to 260 days. Furthermore, insight was obtained into dominant transformation processes as well as the magnitude of chemical inputs to the estuary and their sources. The approach developed shows that under certain conditions, estuaries can be used to quantify the persistence of organic contaminants with half-lives of the order of several months.
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8.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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9.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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10.
  • Chen, Yiqin, et al. (författare)
  • Monthly variation in faeces : blood concentration ratio of persistent organic pollutants over the first year of life
  • 2016
  • Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 147, s. 259-268
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have found that the concentrations of a range of persistent organic pollutants (POPs) in faeces is linearly proportional to the POP concentrations in blood of human adults irrespective of age and gender. In order to investigate the correlation between POP concentrations in faeces and blood in infants, the monthly variation of POP concentrations in faeces over the first year of life of one infant was investigated in this study and compared to modelled blood concentrations. Faecal samples were collected from one male infant daily. The samples were pooled by month and analysed for three selected POPs (2,2',4,4',5,5'-Hexachlorobiphenyl (PCB153), p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and 2,2',4,4'-tetrabromodiphenyl ether (BDE47)). The POP concentrations in faecal samples increased for the first four months by a factor of 2.9, 4.9 and 1.4 for PCB153, BDE47, and p,p'-DDE, respectively. The faecal concentrations of all POPs decreased rapidly following the introduction of formula and solid food to the diet and subsequent weaning of the infant. Further, a one-compartment model was developed to estimate the daily POP concentrations in the blood of the infant. The POP concentrations in blood were predicted to vary much less over the first year than those observed in faeces. The faeces:blood concentration ratio of selected POPs (K-fb) differed significantly (P < 0.0001) between the period before and after weaning, and observed changes in K-fb are far greater than the uncertainty in the estimated K-fb. A more stable K-fb after weaning indicates the possibility of applying the stable K-fb values for non-invasive assessment of internal exposure in infants after weaning. The intra-individual variation in K-fb in infants is worthy of further investigation.
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11.
  • Chen, Yiqin, et al. (författare)
  • Persistent organic pollutants in matched breast milk and infant faeces samples
  • 2015
  • Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 118, s. 309-314
  • Tidskriftsartikel (refereegranskat)abstract
    • Assessing blood concentration of persistent organic pollutants (POPs) in infants is difficult due to the ethical and practical difficulties in obtaining sufficient quantities of blood. To determine whether measuring POPs in faeces might reflect blood concentration during infancy, we measured the concentrations of a range of POPs (i.e. polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs)) in a pilot study using matched breast milk and infant faecal samples obtained from ten mother-child pairs. All infants were breast fed, with 8 of them also receiving solid food at the time of faecal sampling. In this small dataset faecal concentrations (range 0.01-41 ng g(-1) lipid) are strongly associated with milk concentrations (range 0.02-230 ng g(-1) lipid). Associations with other factors generally could not be detected in this dataset, with the exception of a small effect of age or growth. Different sources (external or internal) of exposure appeared to directly influence faecal concentrations of different chemicals based on different inter-individual variability in the faeces-to-milk concentration ratio R-fm. Overall, the matrix of faeces as an external measure of internal exposure in infants looks promising for some chemicals and is worth assessing further in larger datasets.
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12.
  • Clift, Roland, et al. (författare)
  • The Challenges of Applying Planetary Boundaries as a Basis for Strategic Decision-Making in Companies with Global Supply Chains
  • 2017
  • Ingår i: Sustainability. - : MDPI AG. - 2071-1050. ; 9:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The Planetary Boundaries (PB) framework represents a significant advance in specifying the ecological constraints on human development. However, to enable decision-makers in business and public policy to respect these constraints in strategic planning, the PB framework needs to be developed to generate practical tools. With this objective in mind, we analyse the recent literature and highlight three major scientific and technical challenges in operationalizing the PB approach in decision-making: first, identification of thresholds or boundaries with associated metrics for different geographical scales; second, the need to frame approaches to allocate fair shares in the 'safe operating space' bounded by the PBs across the value chain and; third, the need for international bodies to co-ordinate the implementation of the measures needed to respect the Planetary Boundaries. For the first two of these challenges, we consider how they might be addressed for four PBs: climate change, freshwater use, biosphere integrity and chemical pollution and other novel entities. Four key opportunities are identified: (1) development of a common system of metrics that can be applied consistently at and across different scales; (2) setting 'distance from boundary' measures that can be applied at different scales; (3) development of global, preferably open-source, databases and models; and (4) advancing understanding of the interactions between the different PBs. Addressing the scientific and technical challenges in operationalizing the planetary boundaries needs be complemented with progress in addressing the equity and ethical issues in allocating the safe operating space between companies and sectors.
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14.
  • Fazey, Ioan, et al. (författare)
  • Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
  • 2020
  • Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
  • Tidskriftsartikel (refereegranskat)abstract
    • Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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15.
  • Fenner, Kathrin, et al. (författare)
  • Methodological Advances to Study Contaminant Biotransformation : New Prospects for Understanding and Reducing Environmental Persistence?
  • 2021
  • Ingår i: ACS - ES & T Water. - : American Chemical Society (ACS). - 2690-0637. ; 1:7, s. 1541-1554
  • Tidskriftsartikel (refereegranskat)abstract
    • Complex microbial communities in environmental systems play a key role in the detoxification of chemical contaminants by transforming them into less active metabolites or by complete mineralization. Biotransformation, i.e., transformation by microbes, is well understood for a number of priority pollutants, but a similar level of understanding is lacking for many emerging contaminants encountered at low concentrations and in complex mixtures across natural and engineered systems. Any advanced approaches aiming to reduce environmental exposure to such contaminants (e.g., novel engineered biological water treatment systems, design of readily degradable chemicals, or improved regulatory assessment strategies to determine contaminant persistence a priori) will depend on understanding the causal links among contaminant removal, the key driving agents of biotransformation at low concentrations (i.e., relevant microbes and their metabolic activities), and how their presence and activity depend on environmental conditions. In this Perspective, we present the current understanding and recent methodological advances that can help to identify such links, even in complex environmental microbiomes and for contaminants present at low concentrations in complex chemical mixtures. We discuss the ensuing insights into contaminant biotransformation across varying environments and conditions and ask how much closer we have come to designing improved approaches to reducing environmental exposure to contaminants.
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16.
  • Holmes, Michael V., et al. (författare)
  • Mendelian randomization of blood lipids for coronary heart disease
  • 2015
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 36:9, s. 539-539
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. Methods and results We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a priormeta-analysis (threshold P < 2 x 10(-6)); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P <= 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestrictedallele score (48SNPs) was associated with CHD(OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75). Conclusion The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.
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17.
  • Li, Zhe, 1987- (författare)
  • Fate of Pharmaceuticals and Their Transformation Products in Rivers : An integration of target analysis and screening methods to study attenuation processes
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Pharmaceuticals are environmental contaminants causing steadily increasing concern due to their high usage, ubiquitous distribution in the aquatic environment, and potential to exert adverse effects on the ecosystems. After being discharged from wastewater treatment plants (WWTPs), pharmaceuticals can undergo transformation processes in surface waters, of which microbial degradation in river sediments is considered highly significant. In spite of a substantial number of studies on the occurrence of pharmaceuticals in aquatic systems, a comprehensive understanding of their environmental fate is still limited. First of all, very few consistent datasets from lab-based experiments to field studies exist to allow for a straightforward comparison of observations. Secondly, data on the identity and occurrence of transformation products (TPs) is insufficient and the relation of the behavior of TPs to that of their parent compounds (PCs) is poorly understood. In this thesis, these knowledge gaps were addressed by integrating the TP identification using suspect/non-target screening approaches and PC/TP fate determination. The overarching objective was to improve the understanding of the fate of pharmaceuticals in rivers, with a specific focus on water-sediment interactions, and formation and behavior of TPs. In paper I, 11 pharmaceutical TPs were identified in water-sediment incubation experiments using non-target screening. Bench-scale flume experiments were conducted in paper II to simultaneously investigate the behavior of PCs and TPs in both water and sediment compartments under more complex and realistic hydraulic conditions. The results illustrate that water-sediment interactions play a significant role for efficient attenuation of PCs, and demonstrate that TPs are formed in sediment and released back to surface water. In paper III the environmental behavior of PCs along stretches of four wastewater-impacted rivers was related to that of their TPs. The attenuation of PCs is highly compound and site specific. The highest attenuation rates of the PCs were observed in the river with the most efficient river water-pore water exchange. This research also indicates that WWTPs can be a major source of TPs to the receiving waters. In paper IV, suspect screening with a case-control concept was applied on water samples collected at both ends of the river stretches, which led to the identification of several key TPs formed along the stretches. The process-oriented strategies applied in this thesis provide a basis for prioritizing and identifying the critical PCs and TPs with respect to environmental relevance in future fate studies.
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18.
  • McLachlan, Michael S., et al. (författare)
  • Fate of a perfluoroalkyl acid mixture in an agricultural soil studied in lysimeters
  • 2019
  • Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 223, s. 180-187
  • Tidskriftsartikel (refereegranskat)abstract
    • Perfluoroalkyl acids (PFAAs) are environmental contaminants of concern in both food and drinking water. PFAA fate in agricultural soil is an important determinant of PFAA contamination of groundwater and crops. The fate of C4-C14 perfluorinated carboxylic acids (PFCAs) and two perfluorinated sulfonic acids (PFSAs) in an agricultural soil was studied in a field lysimeter experiment. Soil was spiked with PFAAs at four different levels and crops were planted. PFAA concentrations in soil were measured at the beginning and end of the growing season. Lysimeter drainage water was collected and analysed. The concentrations of all PFAAs decreased in the surface soil during the growing season, with the decrease being negatively correlated with the number of fluorinated carbons in the PFAA molecule. PFAA transfer to the drainage water was also negatively correlated with the number of fluorinated carbons. For the C11-C14 PFCAs most of the decrease in soil concentration was attributed to the formation of non-extractable residues. For the remaining PFAAs leaching was the dominant removal process. Leaching was concentration dependent, with more rapid removal from the soils spiked with higher PFAA levels. Model simulations based on measured K-d values under-predicted removal by leaching. This was attributed to mixture effects that reduced PFAA sorption to soil.
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19.
  • McLachlan, Michael S., et al. (författare)
  • Using Model-Based Screening to Help Discover Unknown Environmental Contaminants
  • 2014
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 48:13, s. 7264-7271
  • Tidskriftsartikel (refereegranskat)abstract
    • Of the tens of thousands of chemicals in use, only a small fraction have been analyzed in environmental samples. To effectively identify environmental contaminants, methods to prioritize chemicals for analytical method development are required. We used a high-throughput model of chemical emissions, fate, and bioaccumulation to identify chemicals likely to have high concentrations in specific environmental media, and we prioritized these for target analysis. This model-based screening was applied to 215 organosilicon chemicals culled from industrial chemical production statistics. The model-based screening prioritized several recognized organosilicon contaminants and generated hypotheses leading to the selection of three chemicals that have not previously been identified as potential environmental contaminants for target analysis. Trace analytical methods were developed, and the chemicals were analyzed in air, sewage sludge, and sediment. All three substances were found to be environmental contaminants. Phenyl-tris(trimethylsiloxy)silane was present in all samples analyzed, with concentrations of similar to 50 pg m(-3) in Stockholm air and similar to 0.5 ng g(-1) dw in sediment from the Stockholm archipelago. Tris(trifluoropropyl)trimethyl-cyclotrisiloxane and tetrakis(trifluoropropyl)tetramethyl-cyclotetrasiloxane were found in sediments from Lake Mjosa at similar to 1 ng g(-1) dw. The discovery of three novel environmental contaminants shows that models can be useful for prioritizing chemicals for exploratory assessment.
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20.
  • Schmidt, Amand F., et al. (författare)
  • PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study
  • 2017
  • Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:2, s. 97-105
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA 1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0.09 mmol/L, 95% CI 0.02 to 0.15), bodyweight (1.03 kg, 0.24 to 1.82), waist-to-hip ratio (0.006, 0.003 to 0.010), and an odds ratio for type diabetes of 1.29 (1.11 to 1.50). Based on the collected data, we did not identify associations with HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -0.09 to 0.30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefi ts of PCSK9 inhibitor treatment, as was previously done for statins.
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21.
  • Schmidt, Amand F., et al. (författare)
  • Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
  • 2019
  • Ingår i: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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22.
  • Zou, Hongyan, 1985-, et al. (författare)
  • Temporal Variation of Chemical Persistence in a Swedish Lake Assessed by Benchmarking
  • 2015
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 49:16, s. 9881-9888
  • Tidskriftsartikel (refereegranskat)abstract
    • Chemical benchmarldng was used to investigate the temporal variation of the persistence of chemical contaminants in a Swedish lake. The chemicals studied included 12 pharmaceuticals, an artificial sweetener, and an X-ray contrast agent. Measurements were conducted in late spring, late autumn, and winter. The transformation half-life in the lake could be quantified for 7 of the chemicals. It ranged from several days to hundreds of days. For 5 of the chemicals (bezafibrate, climbazole, diclofenac, furosemide, and hydrochlorothiazide), the measured persistence was lower in late spring than in late autumn. This may have been caused by lower temperatures and/or less irradiation during late autumn. The seasonality in chemical persistence contributed to changes in chemical concentrations in the lake during the year. The impact of seasonality of persistence was compared with the impact of other important variables determining concentrations in the lake: chemical inputs and water flow/dilution. The strongest seasonal variability in chemical concentration in lake water was observed for hydrochlorothiazide (over a factor of 10), and this was attributable to the seasonality in its persistence.
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23.
  • Zou, Hongyan, et al. (författare)
  • Using Chemical Benchmarking to Determine the Persistence of Chemicals in a Swedish Lake
  • 2015
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 49:3, s. 1646-1653
  • Tidskriftsartikel (refereegranskat)abstract
    • It is challenging to measure the persistence of chemicals under field conditions. In this work, two approaches for measuring persistence in the field were compared: the chemical mass balance approach, and a novel chemical benchmarking approach. Ten pharmaceuticals, an X-ray contrast agent, and an artificial sweetener were studied in a Swedish lake. Acesulfame K was selected as a benchmark to quantify persistence using the chemical benchmarking approach. The 95% confidence intervals of the half-life for transformation in the lake system ranged from 780-5700 days for carbamazepine to <1-2 days for ketoprofen. The persistence estimates obtained using the benchmarking approach agreed well with those from the mass balance approach (1-21% difference), indicating that chemical benchmarking can be a valid and useful method to measure the persistence of chemicals under field conditions. Compared to the mass balance approach, the benchmarking approach partially or completely eliminates the need to quantify mass flow of chemicals, so it is particularly advantageous when the quantification of mass flow of chemicals is difficult. Furthermore, the benchmarking approach allows for ready comparison and ranking of the persistence of different chemicals.
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24.
  • Adolfsson-Erici, Margaretha, et al. (författare)
  • A flow-through passive dosing system for continuously supplying aqueous solutions of hydrophobic chemicals to bioconcentration and aquatic toxicity tests
  • 2012
  • Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 86:6, s. 593-599
  • Tidskriftsartikel (refereegranskat)abstract
    • A continuous supply of water with defined stable concentrations of hydrophobic chemicals is a requirement in a range of laboratory tests such as the OECD 305 protocol for determining the bioconcentration factor in fish. Satisfying this requirement continues to be a challenge, particularly for hydrophobic chemicals. Here we present a novel solution based on equilibrium passive dosing. It employs a commercially available unit consisting of similar to 16000 polydimethylsiloxane (PDMS) tubes connected to two manifolds. The chemicals are loaded into the unit by repeatedly perfusing it with a methanol solution of the substances that is progressively diluted with water. Thereafter the unit is perfused with water and the chemicals partition from the unit into the water. The system was tested with nine chemicals with logK(ow) ranging from 4.1 to 6.3. The aqueous concentrations generated were shown to be largely independent of the water flow rate, and the unit to unit reproducibility was within a factor of similar to 2. In continuous flow experiments the aqueous concentrations of most of the study chemicals remained constant over 8 d. A model was assembled that allows prediction of the operating characteristics of the system from the logKow or PDMS/water partition coefficient of the chemical. The system is a simple, safe, predictable and flexible tool that generates stable aqueous concentrations of hydrophobic chemicals.
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25.
  • Adolfsson-Erici, Margaretha, 1950- (författare)
  • Fish bile in environmental analysis
  • 2005
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This work explores the usefulness of fish bile analysis in combination with biomarkers for identifying and evaluating new environmental contaminants in the aquatic environment. It illustrates how bile analysis can be used together with biomarkers to assess the causes of estrogenic effects, to identify chemicals in the aquatic environment that are taken up by fish, and to monitor environmental exposure.In a first application, fish exposed to sewage treatment plant effluent were studied. Elevated levels of vitellogenin in the exposed fish demonstrated that estrogenic effects occurred. Several estrogen disrupting substances were identified in the fish bile, and analysis of water samples confirmed that these substances were present in the effluent. The synthetic estrogen 17a-ethinylestradiol, which is known to be present in sewage treatment plant effluent, was shown for the first time to be taken up by fish. Considering the reported potencies of the detected substances, it was concluded that 17a-ethinylestradiol was the major contributor to the estrogenic effects.Chemical analysis of bile was used to identify rubber additives that were released from tires immersed in water. The bile of rainbow trout held in the water contained high levels of metabolites of PAHs and aromatic nitrogen compounds. Several biomarkers were also measured in the exposed fish, and EROD induction and oxidative stress were observed. Based on the bile analysis observations together with knowledge of toxicological mechanisms, it was postulated that the EROD induction was due to the PAHs, while aromatic nitrogen compounds caused the oxidative stress.Resin acids in fish bile proved to be a good indicator of exposure in a chronic long-term study of rainbow trout exposed to effluent from a total chlorine free (TCF) pulp mill. Elevated levels of GST (gluthatione-S-transferase) and GR (gluthatione reductase) activity, and the presence of DNA adducts after a two month recovery period, indicated that compounds in the pulp mill effluents have persistent effects. In addition to characterising the exposure of the fish to the effluent, the analysis of the resin acids in the bile provided evidence of accidents in the pulp mill that the existing process monitoring system had not detected.Resin acids in bile were also found to be a valuable indicator of exposure to pulp mill effluents for eelpout living in the Baltic Sea. A correlation between resin acid levels in bile and skewed sex ratios provided an important link in the chain of evidence that substances in the pulp mill effluents cause male bias of the eelpout embryos.A particularly good example of the potential of bile analysis was the identification of a previously unknown environmental contaminant. A large peak was observed in the bile extracts of fish that had been exposed to sewage treatment plant effluent. This peak was identified as triclosan, which demonstrated its presence in sewage treatment plant effluent. Other work went on to show that it is a common contaminant of the aquatic environment. The ability of fish to concentrate contaminant metabolites in bile to levels very much higher than in the environment, and the comparatively low levels of analytic interferences, make bile a particularly attractive matrix to search for new, unknown organic pollutants
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26.
  • Adolfsson-Erici, Margaretha, et al. (författare)
  • In-vivo passive sampling to measure elimination kinetics in bioaccumulation tests
  • 2012
  • Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 88:1, s. 62-68
  • Tidskriftsartikel (refereegranskat)abstract
    • The application of in-tissue passive sampling to quantify chemical kinetics in fish bioconcentration experiments was investigated. A passive sampler consisting of an acupuncture needle covered with a PDMS tube was developed together with a method for its deployment in rainbow trout. The time to steady state for chemical uptake into the passive sampler was >1 d, so it was employed as a kinetically limited sampler with a deployment time of 2 h. The passive sampler was employed in parallel with the established whole tissue extraction method to study the elimination kinetics of 10 diverse chemicals in rainbow trout. 4-n-nonylphenol and 2,4,6-tri-tert-butylphenol were close to or below the limit of quantification in the sampler. For chlorpyrifos, musk xylene, hexachlorobenzene, 2,5-dichlorobiphenyl and p,p'-DDT. the elimination rate constants determined with the passive sampler method and the established method agreed within 18%. Poorer agreement (35%) was observed for 2,3,4-trichloroanisole and p-diisopropylbenzene because fewer data were obtained with the passive sampling method due to its lower sensitivity. The work shows that in-tissue passive sampling can be employed to measure contaminant elimination kinetics in fish. This opens up the possibility of studying contaminant kinetics in individual fish, thereby reducing the fish requirements and analytical costs for the determination of bioconcentration factors.
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27.
  • Adolfsson-Erici, Margaretha, et al. (författare)
  • Internal Benchmarking Improves Precision and Reduces Animal Requirements for Determination of Fish Bioconcentration Factors
  • 2012
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 46:15, s. 8205-8211
  • Tidskriftsartikel (refereegranskat)abstract
    • The enactment of new chemical regulations has generated a large need for the measurement of the fish bioconcentration factor (BCF). Past experience shows that the BCF determination lacks precision, requires large numbers of fish, and is costly. A new protocol was tested that shortens the experiment from up to 12 weeks for existing protocols to 2 weeks and reduces the number of fish by a factor of 5, while introducing internal benchmarking for the BCF determination. Rainbow trout were simultaneously exposed to 11 chemicals. The BCFs were quantified using one of the test chemicals, musk xylene, as a benchmark. These were compared with BCFs measured in a parallel experiment based on the OECD 305 guideline. The agreement was <20% for five chemicals and between 20%-25% for two further, while two chemicals lay outside the BCF operating window of the experiment and one was lost due to analytical difficulties. This agreement is better than that observed in a BCF Gold Standard Database. Internal benchmarking allows the improvement of the precision of BCF determination in parallel to large reduction in costs and fish requirements.
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28.
  • Adolfsson-Erici, Margaretha, et al. (författare)
  • Measuring bioconcentration factors in fish using exposure to multiple chemicals and internal benchmarking to correct for growth dilution
  • 2012
  • Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 31:8, s. 1853-1860
  • Tidskriftsartikel (refereegranskat)abstract
    • Modern chemical legislation requires measuring the bioconcentration factor (BCF) of large numbers of chemicals in fish. The BCF must be corrected for growth dilution, because fish growth rates vary between laboratories. Two hypotheses were tested: (1) that BCFs of multiple chemicals can be measured simultaneously in one experiment, and (2) that internal benchmarking using a conservative test substance in the chemical mixture can be used to correct for growth dilution. Bioconcentration experiments were conducted following major elements of the OECD 305 guideline. Fish were simultaneously exposed to 11 chemicals selected to cover a range of BCFs and susceptibility to biotransformation. A method was developed to calculate the growth-corrected elimination rate constant from the concentration ratio of the analyte and a benchmarking chemical for which growth dilution dominated other elimination mechanisms. This method was applied to the experimental data using hexachlorobenzene as the benchmarking chemical. The growth dilution correction lowered the apparent elimination rate constants by between 5% and a factor of four for eight chemicals, while for two chemicals the growth-corrected elimination rate constant was not significantly different from zero. The benchmarking method reduced the uncertainty in the elimination rate constant compared to the existing method for growth dilution correction. The BCFs from exposing fish to 10 chemicals at once were consistent with BCF values from single-chemical exposures from the literature, supporting hypothesis 1. Environ. Toxicol. Chem. 2012; 31: 18531860. (c) 2012 SETAC
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29.
  • af Geijerstam, Peder, Doktorand, 1983-, et al. (författare)
  • Prescription and dispensing duration of medicines for hypertension and other chronic conditions: a review of international policies and evidence to inform the Australian setting
  • 2024
  • Ingår i: Hypertension Research. - : Springer Nature. - 0916-9636 .- 1348-4214.
  • Forskningsöversikt (refereegranskat)abstract
    • The duration of treatment for which a physician may prescribe a medicine, ‘prescription duration’, is often dispensed at the pharmacy on multiple occasions of shorter time periods, ‘dispensing duration’. These durations vary significantly between and within countries. In Australia, the quantity of medication supplied at each dispensing has recently been extended from 30 to 60 days for a selection of medicines used for chronic health conditions, such as diabetes and hypertension. Dispensing durations vary between countries, with 30, 60 or 90 days being the most common—with 90 days aligning with the recommendation of the 2023 Global Report on Hypertension from the World Health Organization. The full impact of shorter vs longer prescription durations on health costs and outcomes is unknown, but current evidence suggests that 90-day dispensing could reduce costs and improve patient convenience and adherence. More rigorous research is needed.
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30.
  • Armitage, James M, et al. (författare)
  • A model assessment of polychlorinated dibenzo-p-dioxin and dibenzofuran sources and fate in the Baltic Sea.
  • 2009
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 407:12, s. 3784-3792
  • Tidskriftsartikel (refereegranskat)abstract
    • The contamination of the Baltic Sea with polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) has resulted in restrictions on the marketing and consumption of Baltic Sea fish, making this a priority environmental issue in the European Union. To date there is no consensus on the relative importance of different sources of PCDD/Fs to the Baltic Sea, and hence no consensus on how to address this issue. In this work we synthesized the available information to create a PCDD/F budget for the Baltic Sea, focusing on the two largest basins, the Bothnian Sea and the Baltic Proper. The non-steady state multimedia fate and transport model POPCYCLING-Baltic was employed, using recent data for PCDD/F concentrations in air and sediment as boundary conditions. The PCDD/F concentrations in water predicted by the model were in good agreement with recent measurements. The budget demonstrated that atmospheric deposition was the dominant source of PCDD/Fs to the basins as a whole. This conclusion was supported by a statistical comparison of the PCDD/F congener patterns in surface sediments from accumulation bottoms with the patterns in ambient air, bulk atmospheric deposition, and a range of potential industrial sources. Prospective model simulations indicated that the PCDD/F concentrations in the water column will continue to decrease in the coming years due to the slow response of the Baltic Sea system to falling PCDD/F inputs in the last decades, but that the decrease would be more pronounced if ambient air concentrations were to drop further in the future, for instance as a result of reduced emissions. The study illustrates the usefulness of using monitoring data and multimedia models in an integrated fashion to address complex organic contaminant issues.
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31.
  • Armitage, James M., 1974- (författare)
  • Modeling the global fate and transport of perfluoroalkylated substances (PFAS)
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Perfluoroalkylated substances (PFAS) are persistent contaminants that are widely distributed in the global environment. Despite the fact that these chemicals have been manufactured and used for over 50 years, there has been little scientific and regulatory interest until very recently. An important research priority over the past decade has been to gain a better understanding of the mechanisms and pathways explaining the presence of these compounds in remote regions. One explanation is related to the use and release of volatile precursor compounds which undergo atmospheric transport and are also susceptible to degradation to PFAS through gas phase reactions with radical species. The main purpose of this doctoral thesis was to investigate an alternative explanation, namely the long-range transport (LRT) of PFAS themselves, which have been released into the environment in substantial quantities during manufacturing and product use. Papers I – III explore the LRT potential of perfluorocarboxylic acids and perfluorocarboxylates and demonstrate that both oceanic and atmospheric transport are efficient pathways of dispersion from source to remote regions of the Northern Hemisphere. Oceanic transport of perfluorooctane sulfonate (PFOS) was shown to be an important process in Paper IV as well. The role of precursor transport and degradation to PFOS was also examined in this paper. The most interesting aspect of the fate and transport of PFOS precursors is the rapid response in ambient concentrations exhibited by these compounds in the model simulations following production phase-out. Since precursor compounds are known to degrade to PFOS in vivo, the modeling results demonstrate that this exposure pathway is a plausible explanation for the declining trends in PFOS concentrations reported for marine mammals in some remote environments.
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32.
  • Armitage, James M, et al. (författare)
  • Modeling the Global Fate and Transport of Perfluorooctanoic Acid (PFOA) and Perfluorooctanoate (PFO) Emitted from Direct Sources Using a Multispecies Mass Balance Model
  • 2009
  • Ingår i: Environmental Science and Technology. - : American Chemical Society. - 0013-936X .- 1520-5851. ; 43:4, s. 1134-1140
  • Tidskriftsartikel (refereegranskat)abstract
    • The global-scale fate and transport processes of perfluorooctanoic acid (PFOA) and perfluorooctanoate (PFO) emitted from direct sources were simulated using a multispecies mass balance model over the period 1950 to 2010. The main goal of this study was to assess the atmospheric and oceanic long-range transport potential of direct source emissions and the implications for the contamination of terrestrial and marine systems worldwide. Consistent with previous modeling studies, ocean transport was found to be the dominant pathway for delivering PFO(A) associated with direct sources to the Arctic marine environment, regardless of model assumptions. The modeled concentrations for surface ocean waters were insensitive to assumptions regarding physical−chemical properties and emission mode of entry and were in reasonable agreement with available monitoring data from the Northern Hemisphere. In contrast, model outputs characterizing atmospheric transport potential were highly sensitive to model assumptions, especially the assumed value of the acid dissociation constant (pKa). However, the complete range of model results for scenarios with different assumptions about partitioning and emissions provide evidence that the atmospheric transport of directly emitted PFO(A) can deliver this substance to terrestrial environments distant from sources. Additional studies in remote or isolated terrestrial systems may provide further insight into the scale of contamination actually attributable to direct sources.
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33.
  • Arnot, Jon A., et al. (författare)
  • Prioritizing Chemicals and Data Requirements for Screening-Level Exposure and Risk Assessment
  • 2012
  • Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 120:11, s. 1565-1570
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Scientists and regulatory agencies strive to identify chemicals that may cause harmful effects to humans and the environment; however, prioritization is challenging because of the large number of chemicals requiring evaluation and limited data and resources. OBJECTIVES: We aimed to prioritize chemicals for exposure and exposure potential and obtain a quantitative perspective on research needs to better address uncertainty in screening assessments. METHODS: We used a multimedia mass balance model to prioritize > 12,000 organic chemicals using four far-field human exposure metrics. The propagation of variance (uncertainty) in key chemical information used as model input for calculating exposure metrics was quantified. RESULTS: Modeled human concentrations and intake rates span approximately 17 and 15 orders of magnitude, respectively. Estimates of exposure potential using human concentrations and a unit emission rate span approximately 13 orders of magnitude, and intake fractions span 7 orders of magnitude. The actual chemical emission rate contributes the greatest variance (uncertainty) in exposure estimates. The human biotransformation half-life is the second greatest source of uncertainty in estimated concentrations. In general, biotransformation and biodegradation half-lives are greater sources of uncertainty in modeled exposure and exposure potential than chemical partition coefficients. CONCLUSIONS: Mechanistic exposure modeling is suitable for screening and prioritizing large numbers of chemicals. By including uncertainty analysis and uncertainty in chemical information in the exposure estimates, these methods can help identify and address the important sources of uncertainty in human exposure and risk assessment in a systematic manner.
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34.
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35.
  • Binnington, Matthew J., et al. (författare)
  • Evaluating the Effectiveness of Fish Consumption Advisories : Modeling Prenatal, Postnatal, and Childhood Exposures to Persistent Organic Pollutants
  • 2014
  • Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 122:2, s. 178-186
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Because human exposure to persistent organic pollutants (POPs) occurs mainly through ingestion of contaminated food, regulatory bodies issue dietary consumption advisories to describe safe intake levels for food items of concern, particularly fish. Objectives: Our study goal was to estimate the effectiveness of fish consumption advisories in reducing exposure of infants and children to POPs. Methods: We used the time-variant mechanistic model CoZMoMAN to estimate and compare prenatal, postnatal, and childhood exposure to polychlorinated biphenyl congener PCB-153 under different scenarios of maternal guideline adherence for both hypothetical constant and realistic time-variant chemical emissions. The scenarios differed in terms of length of compliance (1 vs. 5 years), extent of fish substitution (all vs. half), and replacement diet (uncontaminated produce vs. beef). We also estimated potential exposure reductions for a range of theoretical chemicals to explore how guideline effectiveness varies with a chemical's partitioning and degradation properties. Results: When assuming realistic time periods of advisory compliance, our findings suggest that temporarily eliminating or reducing maternal fish consumption is largely ineffective in reducing pre-and postnatal exposure to substances with long elimination half-lives in humans, especially during periods of decreasing environmental emissions. Substituting fish with beef may actually result in higher exposure to certain groups of environmental contaminants. On the other hand, advisories may be highly effective in reducing exposure to substances with elimination half-lives in humans shorter than the length of compliance. Conclusions: Our model estimates suggest that fish consumption advisories are unlikely to be effective in reducing prenatal, postnatal, and childhood exposures to compounds with long elimination half-lives in humans.
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36.
  • Bolinius, Dämien Johann, et al. (författare)
  • A passive dosing method to determine fugacitycapacities and partitioning properties of leaves
  • 2016
  • Ingår i: Environmental Science. - : Royal Society of Chemistry (RSC). - 2050-7887 .- 2050-7895. ; 18, s. 1325-1332
  • Tidskriftsartikel (refereegranskat)abstract
    • The capacity of leaves to take up chemicals from the atmosphere and water in fl uences how contaminantsare transferred into food webs and soil. We provide a proof of concept of a passive dosing method tomeasure leaf/polydimethylsiloxane partition ratios ( K leaf/PDMS ) for intact leaves, using polychlorinatedbiphenyls (PCBs) as model chemicals. Rhododendron leaves held in contact with PCB-loaded PDMSreached between 76 and 99% of equilibrium within 4 days for PCBs 3, 4, 28, 52, 101, 118, 138 and 180.Equilibrium K leaf/PDMS extrapolated from the uptake kinetics measured over 4 days ranged from 0.075(PCB 180) to 0.371 (PCB 3). The K leaf/PDMS data can readily be converted to fugacity capacities of leaves( Z leaf ) and subsequently leaf/water or leaf/air partition ratios ( K leaf/water and K leaf/air ) using partitioning datafrom the literature. Results of our measurements are within the variability observed for plant/air partitionratios ( K plant/air ) found in the literature. Log K leaf/air from this study ranged from 5.00 (PCB 3) to 8.30(PCB 180) compared to log K plant/air of 3.31 (PCB 3) to 8.88 (PCB 180) found in the literature. The methodwe describe could provide data to characterize the variability in sorptive capacities of leaves that wouldimprove descriptions of uptake of chemicals by leaves in multimedia fate models.
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37.
  • Bolinius, Damien Johann, 1989- (författare)
  • Methods to measure mass transfer kinetics, partition ratios and atmospheric fluxes of organic chemicals in forest systems
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Vegetation plays an important role in the partitioning, transport and fate of hydrophobic organic contaminants (HOCs) in the environment. This thesis aimed at addressing two key knowledge gaps in our understanding of how plants exchange HOCs with the atmosphere: (1) To improve our understanding of the uptake of HOCs into, and transfer through, leaves of different plant species which can significantly influence the transport and fate of HOCs in the environment; and (2) To evaluate an experimental approach to measure fluxes of HOCs in the field. The methods presented in papers I, II and III contribute to increasing our understanding of the fate and transport of HOCs in leaves by offering straightforward ways of measuring mass transfer coefficients through leaves and partition ratios of HOCs between leaves, leaf lipids and lipid standards and reference materials like water, air and olive oil. The passive dosing study in paper III in particular investigated the role of the composition of the organic matter extracted from leaves in determining the capacity of the leaves to hold chemicals and found no large differences between 7 different plant species, even though literature data on leaf/air partition ratios (Kleaf/air) varies over 1-3 orders of magnitude. In paper IV we demonstrated that the modified Bowen ratio method can be extended to measure fluxes of persistent organic pollutants (POPs) if the fluxes do not change direction over the course of the sampling period and are large enough to be measured. This approach thus makes it possible to measure fluxes of POPs that usually require sampling times of days to weeks to exceed method detection limits. The experimental methods described in this thesis have the potential to support improved parameterization of multimedia models, which can then be evaluated against fluxes measured in the field using the modified Bowen ratio approach.
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38.
  • Borga, Katrine, et al. (författare)
  • Consistency in Trophic Magnification Factors of Cyclic Methyl Siloxanes in Pelagic Freshwater Food Webs Leading to Brown Trout
  • 2013
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 47:24, s. 14394-14402
  • Tidskriftsartikel (refereegranskat)abstract
    • Cyclic volatile methyl siloxanes (cVMS) concentrations were analyzed in the pelagic food web of two Norwegian lakes (Mjosa, Randsfjorden), and in brown trout (Salmo trutta) and Arctic char (Salvelinus alpinus) collected in a reference lake (Femunden), in 2012. Lakes receiving discharge from wastewater treatment plants (Mjosa and Randsfjorden) had cVMS concentrations in trout that were up to 2 orders of magnitude higher than those in Femunden, where most samples were close to the limit of quantification (LOO). Food web biomagnification of cVMS in Mjosa and Randsfjorden was quantified by estimation of trophic magnification factors (TMFs). TMF for legacy persistent organic pollutants (POPs) were analyzed for comparison. Both decamethylcyclopentasiloxane (DS) and dodecamethylcyclohexasiloxane (D6) biomagnified with TMFs of 2.9 (2.1-4.0) and 2.3 (1.8-3.0), respectively. Octamethylcyclotetrasiloxane (D4) was below the LOQ in the majority of samples and had substantially lower biomagnification than for D5 and D6. The cVMS TMFs did not differ between the lakes, whereas the legacy POP TMFs were higher in Mjosa than inRandsfjorden. Whitefish had lower cVMS bioaccumulation compared to legacy POPs, and affected the TMF significance for cVMS, but not for POPs. TMFs of D5 and legacy contaminants in Lake Mjosa were consistent with those previously measured in Mjosa.
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39.
  • Borga, Katrine, et al. (författare)
  • Food Web Accumulation of Cyclic Siloxanes in Lake Mjosa, Norway
  • 2012
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 46:11, s. 6347-6354
  • Tidskriftsartikel (refereegranskat)abstract
    • The biomagnification of the cyclic volatile methyl siloxanes octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexatetrasiloxane (D6) was analyzed in the Lake Mjosa food web in Norway from zooplankton and Mysis to planktivorous and piscivorous fish. The trophic magnification factor (TMF) for D5 was determined and compared with TMFs of several legacy contaminants: polychlorinated biphenyl (PCB) congeners 153 and 180, polybrominated diphenyl ether (PBDE) congeners 47 and 99, and p,p'-DDE. D5 showed TMF significantly greater than 1, implying food web biomagnification (TMF = 2.28, CI: 1.22-4.29). This contrasts with two studies that reported TMF < 1, which may reflect variability in TMF between food webs. The Lake Mjosa D5 TMF was sensitive to the species included at the higher trophic level; whole food web TMF differed from TMF excluding smelt (Osmerus eperlanus) or brown trout (Salmo trutta) (TMF-SMELT = 1.62, CI: 0.96-2.72; TMF-TROUT = 3.58, CI: 1.82-7.03). For legacy contaminants (e.g., PCB-153 and PCB-180), the TMFs were less sensitive to the food web composition, and a better model fit was obtained compared to D5. The differences in biomagnification behavior between D5 and the legacy contaminants suggest that the biomagnification of D5 is being governed by species-specific properties such as biotransformation rate or tissue distribution that differ from those of legacy contaminants.
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40.
  • Breivik, Knut, et al. (författare)
  • Added value of the emissions fractions approach when assessing a chemical's potential for adverse effects as a result of long-range transport
  • 2023
  • Ingår i: Environmental Science Advances. - 2754-7000. ; 2:10, s. 1360-1371
  • Tidskriftsartikel (refereegranskat)abstract
    • It is of considerable interest to identify chemicals which may represent a hazard and risk to environmental and human health in remote areas. The OECD POV and LRTP Screening Tool (“The Tool”) for assessing chemicals for persistence (P) and long-range transport potential (LRTP) has been extensively used for combined P and LRTP assessments in various regulatory contexts, including the Stockholm Convention (SC) on Persistent Organic Pollutants (POPs). The approach in The Tool plots either the Characteristic Travel Distance (CTD, in km), a transport-oriented metric, or the Transfer Efficiency (TE, in %), which calculates the transfer from the atmosphere to surface compartments in a remote region, against overall persistence (POV). For a chemical to elicit adverse effects in remote areas, it not only needs to be transported and transferred to remote environmental surface media, it also needs to accumulate in these media. The current version of The Tool does not have a metric to quantify this process. We screened a list of >12 000 high production volume chemicals (HPVs) for the potential to be dispersed, transferred, and accumulate in surface media in remote regions using the three corresponding LRTP metrics of the emission fractions approach (EFA; ϕ1, ϕ2, ϕ3), as implemented in a modified version of The Tool. Comparing the outcome of an assessment based on CTD/TE and POV with the EFA, we find that the latter classifies a larger number of HPVs as having the potential for accumulation in remote regions than is classified as POP-like by the existing approach. In particular, the EFA identifies chemicals capable of accumulating in remote regions without fulfilling the criterion for POV. The remote accumulation fraction of the EFA is the LRTP assessment metric most suited for the risk assessment stage in Annex E of the SC. Using simpler metrics (such as half-life criteria, POV, and LRTP–POV combinations) in a hazard-based assessment according to Annex D is problematic as it may prematurely screen out many of the chemicals with potential for adverse effects as a result of long-range transport.
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41.
  • Breivik, Knut, et al. (författare)
  • Introducing a nested multimedia fate and transport model for organic contaminants (NEM)
  • 2021
  • Ingår i: Environmental Science. - : Royal Society of Chemistry (RSC). - 2050-7887 .- 2050-7895. ; :8
  • Tidskriftsartikel (refereegranskat)abstract
    • Some organic contaminants, including the persistent organic pollutants (POPs), have achieved global distribution through long range atmospheric transport (LRAT). Regulatory efforts, monitoring programs and modelling studies address the LRAT of POPs on national, continental (e.g. Europe) and/or global scales. Whereas national and continental-scale models require estimates of the input of globally dispersed chemicals from outside of the model domain, existing global-scale models either have relatively coarse spatial resolution or are so computationally demanding that it limits their usefulness. Here we introduce the Nested Exposure Model (NEM), which is a multimedia fate and transport model that is global in scale yet can achieve high spatial resolution of a user-defined target region without huge computational demands. Evaluating NEM by comparing model predictions for PCB-153 in air with measurements at nine long-term monitoring sites of the European Monitoring and Evaluation Programme (EMEP) reveals that nested simulations at a resolution of 1° × 1° yield results within a factor of 1.5 of observations at sites in northern Europe. At this resolution, the model attributes more than 90% of the atmospheric burden within any of the grid cells containing an EMEP site to advective atmospheric transport from elsewhere. Deteriorating model performance with decreasing resolution (15° × 15°, 5° × 5° and 1° × 1°), manifested by overestimation of concentrations across most of northern Europe by more than a factor of 3, illustrates the effect of numerical diffusion. Finally, we apply the model to demonstrate how the choice of spatial resolution affect predictions of atmospheric deposition to the Baltic Sea. While we envisage that NEM may be used for a wide range of applications in the future, further evaluation will be required to delineate the boundaries of applicability towards chemicals with divergent fate properties as well as in environmental media other than air.
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42.
  • Breivik, Knut, et al. (författare)
  • Screening organic chemicals in commerce for emissions in the context of environmental and human exposure
  • 2012
  • Ingår i: Journal of Environmental Monitoring. - : Royal Society of Chemistry (RSC). - 1464-0325 .- 1464-0333. ; 14:8, s. 2028-2037
  • Tidskriftsartikel (refereegranskat)abstract
    • Quantitative knowledge of organic chemical release into the environment is essential to understand and predict human exposure as well as to develop rational control strategies for any substances of concern. While significant efforts have been invested to characterize and screen organic chemicals for hazardous properties, relatively less effort has been directed toward estimating emissions and hence also risks. Here, a rapid throughput method to estimate emissions of discrete organic chemicals in commerce has been developed, applied and evaluated to support screening studies aimed at ranking and identifying chemicals of potential concern. The method builds upon information in the European Union Technical Guidance Document and utilizes information on quantities in commerce (production and/or import rates), chemical function (use patterns) and physical-chemical properties to estimate emissions to air, soil and water within the OECD for five stages of the chemical life-cycle. The method is applied to 16 029 discrete substances (identified by CAS numbers) from five national and international high production volume lists. As access to consistent input data remains fragmented or even impossible, particular attention is given to estimating, evaluating and discussing uncertainties in the resulting emission scenarios. The uncertainty for individual substances typically spans 3 to 4 orders of magnitude for this initial tier screening method. Information on uncertainties in emissions is useful as any screening or categorization methods which solely rely on threshold values are at risk of leading to a significant number of either false positives or false negatives. A limited evaluation of the screening method's estimates for a sub-set of about 100 substances, compared against independent and more detailed emission scenarios presented in various European Risk Assessment Reports, highlights that up-to-date and accurate information on quantities in commerce as well as a detailed breakdown on chemical function are critically needed for developing more realistic emission scenarios.
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43.
  • Breivik, Knut, et al. (författare)
  • The Emissions Fractions Approach to Assessing the Long-Range Transport Potential of Organic Chemicals
  • 2022
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:17, s. 11983-11990
  • Tidskriftsartikel (refereegranskat)abstract
    • The assessment of long-range transport potential (LRTP) is enshrined in several frameworks for chemical regulation such as the Stockholm Convention. Screening for LRTP is commonly done with the OECD Pov and LRTP Screening Tool employing two metrics, characteristic travel distance (CTD) and transfer efficiency (TE). Here we introduce a set of three alternative metrics and implement them in the Tool’s model. Each metric is expressed as a fraction of the emissions in a source region. The three metrics quantify the extent to which the chemical (i) reaches a remote region (dispersion, ϕ1), (ii) is transferred to surface media in the remote region (transfer, ϕ2), and (iii) accumulates in these surface media (accumulation, ϕ3). In contrast to CTD and TE, the emissions fractions metrics can integrate transport via water and air, enabling comprehensive LRTP assessment. Furthermore, since there is a coherent relationship between the three metrics, the new approach provides quantitative mechanistic insight into different phenomena determining LRTP. Finally, the accumulation metric, ϕ3, allows assessment of LRTP in the context of the Stockholm Convention, where the ability of a chemical to elicit adverse effects in surface media is decisive. We conclude that the emission fractions approach has the potential to reduce the risk of false positives/negatives in LRTP assessments.
  •  
44.
  • Breivik, Knut, et al. (författare)
  • Towards an understanding of the link between environmental emissions and human body burdens of PCBs using CoZMoMAN
  • 2010
  • Ingår i: Environment International. - Oxford : Elsevier BV. - 0160-4120 .- 1873-6750. ; 36:1, s. 85-91
  • Tidskriftsartikel (refereegranskat)abstract
    • Different factors affect how organic contaminants released into the environment over time distribute and accumulate, enter various food-chains, and potentially cause toxic effects in wildlife and humans. A sound chemical risk assessment thus requires the determination of the quantitative relationship between emissions and human exposure. This study aimed to assess the extent of the quantitative and mechanistic understanding of the link between environmental emissions and human body burdens for polychlorinated biphenyls (PCBs) in the western part of the Baltic Sea drainage basin and to identify any remaining knowledge gaps. An integrated, non-steady state model calculating human body burden from environmental emissions (CoZMoMAN) was created by linking the multi-compartment environmental fate model CoZMo-POP 2 with the human food chain bioaccumulation model ACC-HUMAN. CoZMoMAN predicted concentrations of seven PCB congeners in 11 key model compartments to typically within a factor of 2 to 4 of measured values, although larger discrepancies are noted for soils and humans. We conclude that whereas the most important processes which link emissions of PCBs to human body burdens are quite well understood in this region, some critical knowledge gaps related to the time trend of historical emissions remain to be addressed.
  •  
45.
  • Chen, Chang-Er L., et al. (författare)
  • Deriving in Vivo Bioconcentration Factors of a Mixture of Fragrance Ingredients Using a Single Dietary Exposure and Internal Benchmarking
  • 2018
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 52:9, s. 5227-5235
  • Tidskriftsartikel (refereegranskat)abstract
    • Chemicals in mixtures that are hydrophobic with Log K-OW > 4 are potentially bioaccumulative. Here, we evaluate an abbreviated and benchmarked in vivo BCF measurement methodology by exposing rainbow trout to a mixture of eight test chemicals found in fragrance substances and three benchmark chemicals (musk xylene (MX), hexachlorobenzene (HCB) and PCB52) via a single contaminated feeding event followed by a 28-day depuration period. Concentrations of HCB and PCB52 in fish did not decline significantly (their apparent depuration rate constants, k(T), were close to zero), whereas k(T) for MX was 0.022 d(-1). The test chemicals were eliminated much more rapidly than the benchmark chemicals (k(T) > 0.117 d(-1)). The bioconcentration factors (BCFA) for the test chemicals were in the range of 273 L kg(-1) (8-cyclohexadecen-1-one (globanone)) to 1183 L kg(-1) (alpha-pinene); the benchmarked BCFs (BCFG) calculated relative to HCB ranged from 238 L kg(-1) (globanone) to 1147 L kg(-1) (alpha-pinene). BCFG were not significantly different from BCFA but had smaller standard errors. BCFs derived here agreed well with values previously measured using the OECD 305 test protocol. We conclude that it will be feasible to derive BCFs of chemicals in mixtures using a single dietary exposure and chemical benchmarking.
  •  
46.
  • Chen, Yiqin, et al. (författare)
  • Persistent organic pollutants in infants and toddlers : Relationship between concentrations in matched plasma and faecal samples
  • 2017
  • Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 107, s. 82-88
  • Tidskriftsartikel (refereegranskat)abstract
    • Early-childhood biomonitoring of persistent organic pollutants (POPs) is challenging due to the logistic and ethical limitations associated with blood sampling. We investigated using faeces as a non-invasive matrix to estimate internal exposure to POPs. The concentrations of selected POPs were measured in matched plasma and faecal samples collected from 20 infants/toddlers (aged 13 +/- 4.8 months), including a repeat sample time point for 13 infants (similar to 5 months apart). We observed higher rates of POP quantification in faeces (2 g dry weight) than in plasma (0.5 mL). Among the five chemicals that had quantification frequencies over 50% in both matrices, except for HCB, log concentration in faeces (C-f) and blood (C-b) were correlated (r > 0.74, P < 0.05) for p.p'-dichlorodiphenyldichloroethylene (p,p'-DDE), 2,3', 4,4', 5-pentachlorobiphenyl (PCB118), 2,2', 3,4,4', 5'-pentachlorobiphenyl (PCB138) and 2,2', 4,4', 5,5'-pentachlorobiphenyl (PCB153). We determined faeces: plasma concentration ratios (K-fb), which can be used to estimate C-b from measurements of C-f for infants/toddlers. For a given chemical, the variation in K-fb across individuals was considerable (CV from 0.46 to 0.70). Between 5% and 50% of this variation was attributed to short-term intra-individual variability between successive faecal samples. This variability could be reduced by pooling faeces samples over several days. Some of the remaining variability was attributed to longer-term intra-individual variability, which was consistent with previously reported observations of a decrease in K-fb over the first year of life. The strong correlations between C-f and C-b demonstrate the promise of using faeces for biomonitoring of these compounds. Future research on the sources of variability in K-fb could improve the precision and utility of this technique.
  •  
47.
  • Chirico, Nicola, et al. (författare)
  • In silico approaches for the prediction of the breakthrough of organic contaminants in wastewater treatment plants
  • 2024
  • Ingår i: Environmental Science. - 2050-7887 .- 2050-7895. ; 26:2, s. 400-410
  • Tidskriftsartikel (refereegranskat)abstract
    • The removal efficiency (RE) of organic contaminants in wastewater treatment plants (WWTPs) is a major determinant of the environmental impact of chemicals which are discharged to wastewater. In a recent study, non-target screening analysis was applied to quantify the percentage removal efficiency (RE%) of more than 300 polar contaminants, by analyzing influent and effluent samples from a Swedish WWTP with direct injection UHPLC-Orbitrap-MS/MS. Based on subsets extracted from these data, we developed quantitative structure–property relationships (QSPRs) for the prediction of WWTP breakthrough (BT) to the effluent water. QSPRs were developed by means of multiple linear regression (MLR) and were selected after checking for overfitting and chance relationships by means of bootstrap and randomization procedures. A first model provided good fitting performance, showing that the proposed approach for the development of QSPRs for the prediction of BT is reasonable. By further populating the dataset with similar chemicals using a Tanimoto index approach based on substructure count fingerprints, a second QSPR indicated that the prediction of BT is also applicable to new chemicals sufficiently similar to the training set. Finally, a class-specific QSPR for PEGs and PPGs showed BT prediction trends consistent with known degradation pathways.
  •  
48.
  • Cousins, Anna Palm, 1975- (författare)
  • Environmental fate of chemicals released from consumer products : Multimedia modelling strategies
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The objective of this thesis was to assess the environmental fate and transport of chemicals emitted from consumer products through the development and application of modelling tools. The following hypotheses were tested: i) Multimedia fate models can be applied in a multistage assessment process to emerging chemicals when limited knowledge exists to identify the likely environmental fate and to direct further research; ii) the indoor environment acts as a source of anthropogenic substances in consumer products to the outdoor environment; and iii) chemical removal pathways in the indoor environment are important for the fate of organic chemicals in densely populated areas.The thesis shows that a structured chemical fate assessment strategy can and should be applied at early stages of the evaluation of emerging chemicals to assess their fate and to direct further research. Multimedia fate models play a key role in this strategy. The three‐solubility approach is a simple, rapid method that can be used to estimate physical‐chemical properties for use in early stage evaluation (Paper I). Emissions in the indoor environment affect the urban fate of hydrophobic organic chemicals by providing additional removal pathways and prolonging urban chemical residence times compared to outdoor emissions (Paper III). Emissions of BDE 209, DINP and DEHP to Stockholm indoor air were estimated to be 0.1, 3.4 and 290 mg/capita year, respectively (Paper IV). The contribution of emissions indoors to outdoor air pollution varies between substances. For BDE 209, emissions in the indoor environment added 38 % to the mass entering Stockholm city with inflowing air. For Sweden, the indoor environment was estimated to account for 80 % of BDE 209 emissions to outdoor air (Papers II and IV). For the phthalates, outdoor emissions and/or background inflow are the dominant sources to outdoor air pollution in Stockholm and the influence of the indoor environment is limited (Paper IV).
  •  
49.
  • Cousins, Ian T., et al. (författare)
  • The precautionary principle and chemicals management : The example of perfluoroalkyl acids in groundwater
  • 2016
  • Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 94, s. 331-340
  • Forskningsöversikt (refereegranskat)abstract
    • Already in the late 1990s microgram-per-liter levels of perfluorooctane sulfonate (PFOS) were measured in water samples from areas where fire-fighting foams were used or spilled. Despite these early warnings, the problems of groundwater, and thus drinking water, contaminated with perfluoroalkyl and polyfluoroalkyl substances (PFASs) including PFOS are only beginning to be addressed. It is clear that this PFAS contamination is poorly reversible and that the societal costs of clean-up will be high. This inability to reverse exposure in a reasonable timeframe is a major motivation for application of the precautionary principle in chemicals management. We conclude that exposure can be poorly reversible; 1) due to slow elimination kinetics in organisms, or 2) due to poorly reversible environmental contamination that leads to continuous exposure. In the second case, which is relevant for contaminated groundwater, the reversibility of exposure is not related to the magnitude of a chemical's bioaccumulation potential. We argue therefore that all PFASs entering groundwater, irrespective of their perfluoroalkyl chain length and bioaccumulation potential, will result in poorly reversible exposures and risks as well as further clean-up costs for society. To protect groundwater resources for future generations, society should consider a precautionary approach to chemicals management and prevent the use and release of highly persistent and mobile chemicals such as PFASs. (C) 2016 Elsevier Ltd. All rights reserved.
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50.
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