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Sökning: WFRF:(Gutleb Arno C.)

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1.
  • Minelli, Caterina, et al. (författare)
  • Versailles project on advanced materials and standards (VAMAS) interlaboratory study on measuring the number concentration of colloidal gold nanoparticles
  • 2022
  • Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 14, s. 4690-4704
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe the outcome of a large international interlaboratory study of the measurement of particle number concentration of colloidal nanoparticles, project 10 of the technical working area 34, "Nanoparticle Populations" of the Versailles Project on Advanced Materials and Standards (VAMAS). A total of 50 laboratories delivered results for the number concentration of 30 nm gold colloidal nanoparticles measured using particle tracking analysis (PTA), single particle inductively coupled plasma mass spectrometry (spICP-MS), ultraviolet-visible (UV-Vis) light spectroscopy, centrifugal liquid sedimentation (CLS) and small angle X-ray scattering (SAXS). The study provides quantitative data to evaluate the repeatability of these methods and their reproducibility in the measurement of number concentration of model nanoparticle systems following a common measurement protocol. We find that the population-averaging methods of SAXS, CLS and UV-Vis have high measurement repeatability and reproducibility, with between-labs variability of 2.6%, 11% and 1.4% respectively. However, results may be significantly biased for reasons including inaccurate material properties whose values are used to compute the number concentration. Particle-counting method results are less reproducibile than population-averaging methods, with measured between-labs variability of 68% and 46% for PTA and spICP-MS respectively. This study provides the stakeholder community with important comparative data to underpin measurement reproducibility and method validation for number concentration of nanoparticles.
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2.
  • Covaci, Adrian, et al. (författare)
  • Urinary BPA measurements in children and mothers from six European member states: Overall results and determinants of exposure.
  • 2015
  • Ingår i: Environmental Research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 141:Oct 13, s. 77-85
  • Tidskriftsartikel (refereegranskat)abstract
    • For the first time in Europe, both European-wide and country-specific levels of urinary Bisphenol A (BPA) were obtained through a harmonized protocol for participant recruitment, sampling and quality controlled biomarker analysis in the frame of the twin projects COPHES and DEMOCOPHES. 674 child-mother pairs were recruited through schools or population registers from six European member states (Belgium, Denmark, Luxembourg, Slovenia, Spain and Sweden). Children (5-12y) and mothers donated a urine sample. Information on socio-demographic characteristics, life style, dietary habits, and educational level of the parents was provided by mothers. After exclusion of urine samples with creatinine values below 300mg/L or above 3000mg/L, 653 children and 639 mothers remained for which BPA was measured. The geometric mean (with 95% confidence intervals) and 90th percentile were calculated for BPA separately in children and in mothers and were named "European reference values". After adjustment for confounders (age and creatinine), average exposure values in each country were compared with the mean of the "European reference values" by means of a weighted analysis of variance. Overall geometric means of all countries (95% CI) adjusted for urinary creatinine, age and gender were 2.04 (1.87-2.24) µg/L and 1.88 (1.71-2.07) µg/L for children (n=653) and mothers (n=639), respectively. Multiple regression analysis was used to identify significant environmental, geographical, personal or life style related determinants. Consumption of canned food and social class (represented by the highest educational level of the family) were the most important predictors for the urinary levels of BPA in mothers and children. The individual BPA levels in children were significantly correlated with the levels in their mothers (r=0.265, p<0.001), which may suggest a possible common environmental/dietary factor that influences the biomarker level in each pair. Exposure of the general European population was well below the current health-based guidance values and no participant had BPA values higher than the health-based guidance values.
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3.
  • Gutleb, Arno C., et al. (författare)
  • Effects on bone tissue in ewes (Ovies aries) and their foetuses exposed to PCB 118 and PCB 153
  • 2010
  • Ingår i: Toxicology Letters. - : Elsevier BV. - 0378-4274 .- 1879-3169. ; 192:2, s. 126-133
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the present study was to investigate whether low levels of mono-ortho PCB 118 and di-ortho PCB 153, affect bone composition and strength in ewes (Dala breed) and their foetuses following exposure starting at conception and ending a week before expected delivery. In male foetuses, trabecular bone mineral content at the metaphysis was almost 30% lower in the PCB 118 (49mug/kg body wt/day) group compared to the control group (corn oil) (ANCOVA, P<0.05). In female foetuses of the PCB 153 (98mug/kg body wt/day) group trabecular cross-sectional area at the metaphysis was 19% smaller than in the controls (ANCOVA, P<0.05). At the diaphysis a smaller marrow cavity area (up to 24% reduction) was observed in female and male foetuses exposed to PCB 153 compared with controls (ANCOVA, P<0.05). There were also significant differences at the mid diaphyseal measure point between the PCB 153 and the control group females (ANCOVA, P<0.05). Cortical and total bone mineral density, cortical thickness were significantly higher, endosteal circumference shorter and marrow cavity significantly smaller in the PCB 153 group (ANCOVA, P<0.05). In conclusion there were gender dependent effects on bone tissue and cortical bone was more affected than trabecular bone.
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4.
  • Gutleb, Arno C., et al. (författare)
  • In Vitro Assay Shows That PCB Metabolites Completely Saturate Thyroid Hormone Transport Capacity in Blood of Wild Polar Bears (Ursus maritimus)
  • 2010
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 44:8, s. 3149-3154
  • Tidskriftsartikel (refereegranskat)abstract
    • Persistent chemicals accumulate in the arctic environment due to their chemical reactivity and physicochemical properties and polychlorinated biphenyls (PCBs) are the most concentrated pollutant class in polar bears (Ursus maritimus). Metabolism of PCB and polybrominated biphenyl ether (PBDE) flame-retardants alter their toxicological properties and these metabolites are known to interfere with the binding of thyroid hormone (TH) to transthyretin (TTR) in rodents and humans. In polar bear plasma samples no binding of [I-125]-T-4 to TTR was observed after incubation and PAGE separation. Incubation of the plasma samples with (C-14)-4-OH-CB107, a compound with a higher binding affinity to TTR than the endogenous ligand T-4 resulted in competitive binding as proven by the appearance of a radio labeled TTR peak in the gel. Plasma incubation with T-4 up to 1 mM, a concentration that is not physiologically relevant anymore did not result in any visible competition. These results give evidence that the binding sites on TTR for T-4 in wild living polar bears are completely saturated. Such saturation of binding sites can explain observed lowered levels of THs and could lead to contaminant transport into the developing fetus.
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5.
  • Keune, Hans, et al. (författare)
  • We’re only in it for the knowledge? : a problem solving turn in environment and health expert elicitation
  • 2012
  • Ingår i: Environmental Health. - 1476-069X. ; 11:Supplement 1, s. S3-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The FP6 EU HENVINET project aimed at synthesizing the scientific information available on a number of topics of high relevance to policy makers in environment and health. The goal of the current paper is to reflect on the methodology that was used in the project, in view of exploring the usefulness of this and similar methodologies to the policy process. The topics investigated included health impacts of the brominated flame retardants decabrominated diphenylether (decaBDE) and hexabromocyclododecane (HBCD), phthalates highlighting di(2-ethylhexyl)phthalate (DEHP), the pesticide chlorpyrifos (CPF), nanoparticles, the impacts of climate change on asthma and other respiratory disorders, and the influence of environment health stressors on cancer induction. Methods: Initially the focus was on identifying knowledge gaps in the state of the art in scientific knowledge. Literature reviews covered all elements that compose the causal chain of the different environmental health issues from emissions to exposures, to effects and to health impacts. Through expert elicitation, knowledge gaps were highlighted by assessing expert confidence using calibrated confidence scales. During this work a complementary focus to that on knowledge gaps was developed through interdisciplinary reflections. By extending the scope of the endeavour from only a scientific perspective, to also include the more problem solving oriented policy perspective, the question of which kind of policy action experts consider justifiable was addressed. This was addressed by means of a questionnaire. In an expert workshop the results of both questionnaires were discussed as a basis for policy briefs. Results: The expert elicitation, the application of the calibrated confidence levels and the problem solving approach were all experienced as being quite challenging for the experts involved, as these approaches did not easily relate to mainstream environment and health scientific practices. Even so, most experts were quite positive about it. In particular, the opportunity to widen one's own horizon and to interactively exchange knowledge and debate with a diversity of experts seemed to be well appreciated in this approach. Different parts of the approach also helped in focussing on specific relevant aspects of scientific knowledge, and as such can be considered of reflective value. Conclusions: The approach developed by HENVINET was part of a practice of learning by doing and of interdisciplinary cooperation and negotiation. Ambitions were challenged by unforeseen complexities and difference of opinion and as no Holy Grail approach was at hand to copy or follow, it was quite an interesting but also complicated endeavour. Perfection, if this could be defined, seemed out of reach all the time. Nevertheless, many involved were quite positive about it. It seems that many felt that it fitted some important needs in current science when addressing the needs of policy making on such important issues, without anyone really having a clue on how to actually do this. Challenging questions remain on the quality of such approach and its product. Practice tells us that there probably is no best method and that the best we can do is dependent on contextual negotiation and learning from experiences that we think are relevant.
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6.
  • Lopes, Viviana R, et al. (författare)
  • Dose-dependent autophagic effect of titanium dioxide nanoparticles in human HaCaT cells at non-cytotoxic levels
  • 2016
  • Ingår i: Journal of Nanobiotechnology. - : Springer Science and Business Media LLC. - 1477-3155. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Interactions between nanoparticles and cells are now the focus of a fast-growing area of research. Though many nanoparticles interact with cells without any acute toxic responses, metal oxide nanoparticles including those composed of titanium dioxide (TiO2-NPs) may disrupt the intracellular process of macroautophagy. Autophagy plays a key role in human health and disease, particularly in cancer and neurodegenerative diseases. We herein investigated the in vitro biological effects of TiO2-NPs (18 nm) on autophagy in human keratinocytes (HaCaT) cells at non-cytotoxic levels. Results: TiO2-NPs were characterized by transmission electron microscopy (TEM) and dynamic light scattering techniques. Cellular uptake, as evaluated by TEM and NanoSIMS revealed that NPs internalization led to the formation of autophagosomes. TiO2-NPs treatment did not reduce cell viability of HaCaT cells nor increased oxidative stress. Cellular autophagy was additionally evaluated by confocal microscopy using eGFP-LC3 keratinocytes, western blotting of autophagy marker LC3I/II, immunodetection of p62 and NBR1 proteins, and gene expression of LC3II, p62, NBR1, beclin1 and ATG5 by RT-qPCR. We also confirmed the formation and accumulation of autophagosomes in NPs treated cells with LC3-II upregulation. Based on the lack of degradation of p62 and NBR1 proteins, autophagosomes accumulation at a high dose (25.0 mu g/ml) is due to blockage while a low dose (0.16 mu g/ml) promoted autophagy. Cellular viability was not affected in either case. Conclusions: The uptake of TiO2-NPs led to a dose-dependent increase in autophagic effect under non-cytotoxic conditions. Our results suggest dose-dependent autophagic effect over time as a cellular response to TiO2-NPs. Most importantly, these findings suggest that simple toxicity data are not enough to understand the full impact of TiO2-NPs and their effects on cellular pathways or function.
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7.
  • Lyche, Jan L., et al. (författare)
  • Reproductive and developmental toxicity of phthalates
  • 2009
  • Ingår i: Journal of toxicology and environmental health. Part B, Critical reviews. - : Informa UK Limited. - 1093-7404 .- 1521-6950. ; 12:4, s. 225-249
  • Tidskriftsartikel (refereegranskat)abstract
    • The purposes of this review are to (1) evaluate human and experimental evidence for adverse effects on reproduction and development in humans, produced by exposure to phthalates, and (2) identify knowledge gaps as for future studies. The widespread use of phthalates in consumer products leads to ubiquitous and constant exposure of humans to these chemicals. Phthalates were postulated to produce endocrine-disrupting effects in rodents, where fetal exposure to these compounds was found to induce developmental and reproductive toxicity. The adverse effects observed in rodent models raised concerns as to whether exposure to phthalates represents a potential health risk to humans. At present, di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), and butyl benzyl phthalate (BBP) have been demonstrated to produce reproductive and developmental toxicity; thus, this review focuses on these chemicals. For the general population, DEHP exposure is predominantly via food. The average concentrations of phthalates are highest in children and decrease with age. At present, DEHP exposures in the general population appear to be close to the tolerable daily intake (TDI), suggesting that at least some individuals exceed the TDI. In addition, specific high-risk groups exist with internal levels that are several orders of magnitude above average. Urinary metabolites used as biomarkers for the internal levels provide additional means to determine more specifically phthalate exposure levels in both general and high-risk populations. However, exposure data are not consistent and there are indications that secondary metabolites may be more accurate indicators of the internal exposure compared to primary metabolites. The present human toxicity data are not sufficient for evaluating the occurrence of reproductive effects following phthalate exposure in humans, based on existing relevant animal data. This is especially the case for data on female reproductive toxicity, which are scarce. Therefore, future research needs to focus on developmental and reproductive endpoints in humans. It should be noted that phthalates occur in mixtures but most toxicological information is based on single compounds. Thus, it is concluded that it is important to improve the knowledge of toxic interactions among the different chemicals and to develop measures for combined exposure to various groups of phthalates.
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