| 1. |
- Wiberg, Karin, et al.
(författare)
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Model Selection and Evaluation for Risk Assessment of Dioxin-contaminated Sites
- 2007
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Ingår i: AMBIO: A Journal of the Human Environment. ; 36:6, s. 458-66
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Tidskriftsartikel (refereegranskat)abstract
- The general European population has a total intake of dioxins and dioxin-like chemicals near the limit recommended by the European Union, making additional exposure above background levels undesirable. For populations living near dioxin-contaminated sites, additional exposure may occur by intake of locally produced food, inhalation of particles, dermal contact with soils, or other exposure pathways. Risk assessment tools are required to estimate risks associated with contaminated sites and to set priorities for site remediation. Here, we review several multimedia models that can be applied as tools to support risk assessment. We then present a strategy to select, apply, evaluate, and adapt a model to address a specific situation. The case study we consider is a risk assessment of generic background dioxin exposure in Sweden, and we compare the predictions with environmental observations and exposure data from Sweden. Arguments are presented for selecting the CalTOX model for this case study. We demonstrate the application, evaluation, and adaptation of the model and discuss the requirements for extending the analysis to conduct risk assessment for subpopulations living near dioxin-contaminated sites.
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| 2. |
- Åberg, Annika, et al.
(författare)
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Exposure assessment at a PCDD/F contaminated site in Sweden : field measurements of exposure media and serum analysis
- 2010
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Ingår i: Environmental Science and Pollution Research. - Berlin / Heidelberg : Springer. - 0944-1344 .- 1614-7499. ; 17:1, s. 26-39
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND, AIM, AND SCOPE: The main pathway for human exposure to the highly toxic polychlorinated-p-dioxins and polychlorinated furans [polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs)] is via dietary intake. Other exposure pathways may, however, be important in close proximity to point sources, such as wood preservation sites, where PCDD/F contaminated chlorophenols (CP) were previously used. In this study, a heavily PCDD/F contaminated CP saw mill site in Sweden was investigated. Human exposure through a broad spectrum of exposure pathways was assessed. Such studies are in demand since the question whether contaminated sites represent a current or future risk can only be answered by detailed site-specific risk assessments. MATERIALS AND METHODS: Sampling of exposure media (soil, air, groundwater, raspberries, carrots, potatoes, grass, milk, eggs, and chicken fodder) was made. Exposure media concentrations and congener distribution patterns were used to investigate the mobilization of PCDD/Fs from soil to the environment and to calculate exposure levels for adults. Blood serum levels from site-exposed and control individuals were also analyzed. RESULTS: Congener distribution patterns at the site were generally dominated by a specific marker congener (1234678-HpCDF), which is highly abundant in the polluted soil. The dioxin toxic equivalents (TEQ) concentrations were notably elevated as compared to national reference samples for most exposure media, and the marker congener was a major contributor to increased TEQ levels. There were also indications of soil-to-air volatilization of tetra- and penta-CDD/Fs. People who participated in the restoration of a contaminated building showed higher levels of 1234678-HpCDF compared to controls, and calculated exposure levels suggest that several site-specific exposure routes may be of importance for the daily intake of PCDD/F. CONCLUSIONS, RECOMMENDATIONS, AND PERSPECTIVES: Despite low mobility of higher chlorinated PCDD/Fs, these contaminants were transferred from the polluted soil to the surroundings and into human tissue. The extent of increased exposure from contaminated sites depends on the PCDD/F source strength of the soil, composition of the pollution, human activities, and dietary patterns of the residents. Impact from the contaminated soil on other exposure media was seen also for areas with low to moderate soil contamination. In the future, not only the levels of PCDD/F soil pollution but also the composition must be considered in risk assessments of contaminated sites.
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| 3. |
- Åberg, Annika, et al.
(författare)
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Hälsoriskbedömning av exponering relaterad till dioxinförorenad mark
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sammanfattning I två projekt som har finansierats av kunskapsprogrammet Hållbar Sanering har en kombinerad spridnings- och exponeringsmodell (CalTOX) utvärderats som ett verktyg för riskbedömning av dioxinförorenad mark. Modellens styrka jämfört med liknande modeller är dels att den inkluderar livsmedelsbaserade exponeringsvägar, dels att den kan hantera både bakgrundshalter i luft i kombination med förhöjda halter i marken samt att den är anpassad för att beskriva förändringar över tiden (dynamiska situationer). En initial utvärdering av modellen gjordes med ett generellt bakgrundscenario där modellresultaten jämfördes mot svenska mätdata. I en andra fas utvärderades modellen i ett platsspecifikt förorenad markscenario, där analyser av fältprover på ett dioxinförorenat område utgjorde basen för att kunna avgöra modellens användbarhet ur riskbedömningssynpunkt. De övergripande erfarenheterna som erhållits då CalTOX har tillämpats för beräkningar av dioxinhalter i olika delar av miljön har sammanställts i tabell A och B. Syftet med sammanställningarna är att ge en vägledning av förväntade resultat från modellen samt att visa på hur omständigheter i både modelleringen och utvärderingen som kan leda till avvikelser. Som grund för utvärderingen användes uppmätta halter i miljöprover som ”sanna” värden. En avvikelse på 1-4 gånger mellan uppmätta och beräknade halter betraktades som bra, 5-9 gånger som godkänd och >10 som tveksam. Eftersom avvikelserna mellan beräknade och uppmätta halter varierade för olika kongener var den slutliga bedömningen ändå något subjektiv. Vid slutbedömningen vägdes även exponeringens betydelse in. Dessutom bedömdes en överskattning lindrigare än en underskattning eftersom den senare leder till en underskattad exponeringsrisk. I tabell A återfinns utvärderingen av Bakgrundsscenariot, d.v.s. det scenario som förutsatte svenska bakgrundsnivåer och som är utvärderat med hjälp av analysdata från typiska svenska bakgrundsbelastade prover. Eftersom mätdata för både luft och mark utgjorde ingångsvärden till bakgrundsscenariot har modellresultat för dessa medier ej inkluderats i tabell A. De övergripande erfarenheterna som gjorts då CalTOX tillämpades för ett förorenad markscenario har sammanställts i tabell B. Sediment, ytvatten och fisk uteslöts från utvärderingen eftersom det detaljkunskap om det akvatiska systemet saknades för den specifika platsen. Utvärderingen av CalTOX har visat att verktyget är användbart för att bedöma spridningen av dioxiner till omgivande miljö, både i syfte att återspegla en bakgrundssituation och en situation med förorenad mark. Med hjälp av modellberäkningar har bidraget från flera olika exponeringsvägar jämförts i olika scenarier med ökande koncentration av dioxiner i marken. De exponeringsvägar som uppenbart kan ge en ett väsentligt bidrag till en ökad yttre exponering om marken är förorenad är; • intag av jord • intag av ägg • intag av mjölk • intag av kött • intag av ovanjordiska växter 8HÅLLBAR SANERING Rapport 5929 - Hälsoriskbedömning av exponering relaterad till dioxinförorenad mark • intag av underjordiska växter • hudkontakt med jord Tabell A. Sammanfattning av övergripande erfarenheter från modellberäkningar som erhölls då CalTOX tillämpades på ett bakgrundsscenario. Som grund för utvärderingen användes uppmätta halter i miljöprover som ”sanna” värden. En avvikelse på 1-4 gånger mellan uppmätta och beräknade halter betraktades som bra, 5-9 gånger som godkänd och >10 som tveksam. Tabellen bör endast betraktas som en vägledning av förväntat resultat från en modellering. För förklaring and kommentarer till fotnoter, se kapitel 6.1. Ovanjordiska Underjordiska Ytvatten Grundvatten Sediment växtdelar växtdelar a b Överensstämmelse Bra Godkänd Tveksamc d Bra EA Risk för överskattning xdRisk för underskattning xa xb xc xdKött Mjölk Ägg Fisk e e Överensstämmelse Bra Bra Tveksamf g GodkändRisk för överskattning xe xe xfRisk för underskattning xe xe xf xgTabell B Sammanfattning av övergripande erfarenheter från modellberäkningar som erhölls då CalTOX tillämpades på förorenad markscenario. Som grund för utvärderingen användes platsspecifika uppmätta halter som ”sanna” värden. En avvikelse på 1-4 gånger mellan uppmätta och beräknade halter betraktades som bra, 5-9 gånger som godkänd och >10 som tveksam. Tabellen bör endast betraktas som en vägledning av förväntat resultat från en modellering. Överensstämmelsen är en sammanvägd bedömning av avvikelser mellan modellscenariot/ verkligheten och konsekvenser av avvikelserna. Avvikelser som ger en viss (om än rimlig) säkerhetsmarginal i t.ex. exponeringsberäkningarna har bedömts som godkända. För förklaring och kommentarer till fotnoter, se kapitel 6.1. Ovanjordiska Underjordiska Luft Ytvatten Grundvatten växtdelar växtdelar a Överensstämmelse Godkänd EA Godkändb c d Godkänd GodkändRisk för överskattning xa xb xcRisk för underskattning xdKött Mjölk Ägg f e Överensstämmelse EA Bra TveksamfRisk för överskattning xe xfRisk för underskattning xfFigur A sammanfattar kritiska exponeringsvägar vid olika grad av dioxinförorenad jord identifierade med CalTOX. Intag av animaliska livsmedel (t.ex. kött, mjölk och ägg) som producerats på förorenad mark står sannolikt för de största potentiella exponeringsriskerna eftersom fettinnehållet i dessa produkter bidrar till att dioxiner ackumuleras i dessa produkter. Redan vid låga markkoncentrationer kan livsmedlen kontamineras i relativt hög utsträckning. Områden som förorenats diffust eller som har fläckvis förhöjda halter kan därför utgöra en större risk än ett begränsat hot-spot område där ringa aktivitet pågår. Förorenade objekt med nära läge till betesmarker eller äggproduktion bör således ges hög prioritet vid miljöutredningar. Sannolikt är det spridning av förorenade jordpartiklar till betesväxters bladytor samt direkt intag av förorenad jord vid betning som bidrar till att djuren exponeras. Förhöjda halter av dioxiner i luft och växter (utan jordpartiklar) bidrar i lägre utsträckning. 9HÅLLBAR SANERING Rapport 5929 - Hälsoriskbedömning av exponering relaterad till dioxinförorenad mark 10 100 1000ng TEQ/kg TS i jord Intag av kött/mjölk/ägg Intag av jord Intag av rotfrukter/grönsaker Inhalering av utomhusluft Hudkontakt jord Intag av grundvatten Figur A. Kritiska exponeringsvägar vid olika grad av dioxinförorenad jord identifierade med CalTOX modellering. Antaganden av tillgänglighet: 3 % för hudkontakt, 50 % för intag av jord, samt 100 % för övriga exponeringsvägar. Utöver att fettfraktionen bidrar till att ackumulera dioxiner i mjölk, kött, ägg och andra animaliska livsmedel bidrar den också till att öka tillgängligheten av dioxinerna i magtarmkanalen. Intag av föroreningar via en fettfraktion, t.ex. genom att äta animalisk föda, resulterar i ett större upptag av föroreningarna jämfört med om intaget sker via intag av förorenade partiklar (t.ex. damm eller jord). Intag av jord kan ge ett väsentligt bidrag om markkoncentrationerna är höga. Då jord är den bärande matrisen bör dock hänsyn tas till den lägre tillgängligheten för upptag jämfört med andra matriser (t.ex. livsmedel). Vid bakgrundskoncentrationer i miljön ger intag av jord inget väsentligt bidrag till exponeringen. Exponeringsrisker vid intag av bär och grönsaker från ett förorenat område beror på damm och jord som fastnar på ytorna. Rotupptag och upptag av gasfas från luften är av mindre betydelse. Risker genom intag av bär och grönsaker kan därmed minskas genom att skölja produkterna. Vissa rotfrukter, som morötter, kan ta upp dioxiner i relativt hög utsträckning medan andra rotfrukter, som potatis, tar upp betydligt mindre. Eftersom dioxinerna framförallt anrikas i skalen kan exponeringsriskerna minskas betydligt om produkterna skalas. Hudkontakt kan ge ett väsentligt bidrag till exponeringen om markkoncentrationen är hög. Hur ofta och hur länge man exponeras via hudkontakt samt den hudyta som utsätts för exponeringen är dock avgörande för denna exponeringsvägs betydelse. Hänsyn måste också tas till den markant lägre tillgängligheten för absorbering genom huden då jord är den bärande matrisen. I de generaliserade scenarier som använts befanns inhalering utomhus och intag vatten ej utgöra väsentliga exponeringsvägar. Inhalering torde dock kunna utgöra en exponeringsrisk i byggnader som innehåller förorenat damm och partiklar, t.ex. vid renoveringsarbete i kontaminerade lokaler. 10HÅLLBAR SANERING Rapport 5929 - Hälsoriskbedömning av exponering relaterad till dioxinförorenad mark Erfarenheterna från detta projekt visar att bidraget från en exponeringsväg kan variera kraftigt från situation till situation och att bidraget är starkt beroende av de olika antaganden som görs när exponeringen modelleras. För att få en bra uppfattning om vilka risker som är styrande bör dessa givetvis motsvara den verkliga situationen så långt det är möjligt. Fördelen med att modellera exponeringsriskerna i CalTOX är att varje given situation kan bedömas utifrån en helhet och man kan tydliggöra vilka spridnings- och upptagsvägar som kan bidra till en väsentlig påverkan på omgivningen. För varje exponeringsväg är det möjligt att se vilket medium (t.ex. luft, jord, grundvatten, etc.) som bidrar mest till exponeringsdosen. Detta innebär att en situation där risker för förhöjd exponering föreligger kan detaljstuderas. Eftersom bakgrundshalter kan inkluderas i form av t.ex. luftemissioner och markkoncentr
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| 4. |
- Beronius, Anna, et al.
(författare)
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Bridging the gap between academic research and regulatory health risk assessment of Endocrine Disrupting Chemicals
- 2014
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Ingår i: Current opinion in pharmacology (Print). - : Elsevier BV. - 1471-4892 .- 1471-4973. ; 19, s. 99-104
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory risk assessment is traditionally based primarily on toxicity studies conducted according to standardized and internationally validated test guidelines. However, health risk assessment of endocrine disrupting chemicals (EDCs) is argued to rely on the efficient integration of findings from academic research. The aim of this review was to provide an overview of current developments to facilitate the use of academic research in regulatory risk assessment of chemicals and how certain aspects of study design and reporting are particularly important for the risk assessment process. By bridging the gap between academic research and regulatory health risk assessment of EDCs, scientific uncertainty in risk assessment conclusions can be reduced, allowing for better targeted policy decisions for chemical risk reduction.
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| 5. |
- Beronius, Anna, et al.
(författare)
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Facilitating the use of non-standard in vivo studies in health risk assessment of chemicals : a proposal to improve evaluation criteria and reporting
- 2014
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Ingår i: Journal of Applied Toxicology. - : Wiley. - 0260-437X .- 1099-1263. ; 34:6, s. 607-617
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Tidskriftsartikel (refereegranskat)abstract
- To improve data availability in health risk assessment of chemicals and fill information gaps there is a need to facilitate the use of non-standard toxicity studies, i.e. studies not conducted according to any standardized toxicity test guidelines. The purpose of this work was to propose criteria and guidance for the evaluation of reliability and relevance of non-standard in vivo studies, which could be used to facilitate systematic and transparent evaluation of such studies for health risk assessment. Another aim was to propose user friendly guidance for reporting of non-standard studies intended to promote an improvement in reporting of studies that could be of use in risk assessment. Requirements and recommendations for the design and execution of in vivo toxicity studies were identified from The Organisation for Economic Co-operation and Development (OECD) test guidelines, and served as basis for the data evaluation criteria and reporting guidelines. Feedback was also collected from experts within the field of toxicity testing and risk assessment and used to construct a two-tiered framework for study evaluation, as well as refine the reporting guidelines. The proposed framework emphasizes the importance of study relevance and an important aspect is to not completely dismiss studies from health risk assessment based on very strict criteria for reliability. The suggested reporting guidelines provide researchers with a tool to fulfill reporting requirements as stated by regulatory agencies. Together, these resources provide an approach to include all relevant data that may fill information gaps and reduce scientific uncertainty in health risk assessment conclusions, and subsequently also in chemical policy decisions.
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| 6. |
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| 7. |
- Beronius, Anna, et al.
(författare)
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Health risk assessment procedures for endocrine disrupting compounds within different regulatory frameworks in the European Union
- 2009
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier BV. - 0273-2300 .- 1096-0295. ; 55:2, s. 111-122
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Tidskriftsartikel (refereegranskat)abstract
- In this study we have investigated how different regulatory frameworks in Europe cope with identification and risk assessment of endocrine disrupting compounds (EDCs). Four regulatory groups were selected for the investigation: existing industrial chemicals, environmental pollutants in food, pharmaceuticals and plant protection products. The legislation and guidelines for each of these groups were scrutinized and compared in detail. In addition, one recent European risk assessment document each for three identified EDCs, i.e. bisphenol A, dioxins and vinclozolin, were reviewed and compared. We found that the requirements for toxicity testing and availability and scope of risk assessment guidelines varied between the four regulatory frameworks. Also, the general principles regarding the human relevance of the mode of action identified in animal tests differed in the different risk assessments. In conclusion, there is little conformity in the risk assessment processes between these groups of chemicals. Because of the complicated nature of endocrine disruption, test methods, principles and criteria for data interpretation traditionally used might not be directly applicable to EDCs and further development of a transparent and reliable risk assessment process for this type of substances is needed.
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| 8. |
- Beronius, Anna, et al.
(författare)
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Risk to all or none? A comparative analysis of controversies in the health risk assessment of Bisphenol A
- 2010
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 29:2, s. 132-146
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Tidskriftsartikel (refereegranskat)abstract
- Bisphenol A (BPA) is an endocrine disruptor for which health risk assessment has proven controversial. Conclusions regarding health risks of BPA vary between assessments from "there is no risk to any part of the population" to "there is risk to the entire population". We have carried out a literature study investigating what might be the scientific and/or policy-related reasons for these differences. Ten risk assessments for BPA were scrutinized and several factors were compared between assessments, including estimations of exposure levels, identification of critical study and NOAEL, assessment factors and significance attributed to reports of low-dose effects. Differences in conclusions were mainly influenced by the evaluation of low-dose effects and the uncertainties surrounding the significance of these data for health risk assessment. The results illustrate the impact of differences in risk assessment policy and expert judgment on the risk assessment process and highlight the importance of transparency in this process.
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| 9. |
- Beronius, Anna, et al.
(författare)
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Testing and refining the Science in Risk Assessment and Policy (SciRAP) web-based platform for evaluating the reliability and relevance of in vivo toxicity studies
- 2018
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Ingår i: Journal of Applied Toxicology. - : Wiley. - 0260-437X .- 1099-1263. ; 38:12, s. 1460-1470
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Tidskriftsartikel (refereegranskat)abstract
- The Science in Risk Assessment and Policy (SciRAP) web-based platform was developed to promote and facilitate structure and transparency in the evaluation of ecotoxicity and toxicity studies for hazard and risk assessment of chemicals. The platform includes sets of criteria and a colour-coding tool for evaluating the reliability and relevance of individual studies. The SciRAP method for evaluating in vivo toxicity studies was first published in 2014 and the aim of the work presented here was to evaluate and develop that method further. Toxicologists and risk assessors from different sectors and geographical areas were invited to test the SciRAP criteria and tool on a specific set of in vivo toxicity studies and to provide feedback concerning the scientific soundness and user-friendliness of the SciRAP approach. The results of this expert assessment were used to refine and improve both the evaluation criteria and the colour-coding tool. It is expected that the SciRAP web-based platform will continue to be developed and enhanced to keep up to date with the needs of end-users.
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| 10. |
- Beronius, Anna, et al.
(författare)
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The influence of study design and sex-differences on results from developmental neurotoxicity studies of bisphenol A, implications for toxicity testing
- 2013
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Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 311:1-2, s. 13-26
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Tidskriftsartikel (refereegranskat)abstract
- Developmental neurotoxicity (DNT) of bisphenol A (BPA) has been investigated in a large number of studies. However, there are discrepancies in the results reported between the studies. The aim of this study was to identify and analyze factors that may contribute to these differences and to assess whether there are sex-differences in the sensitivity of certain endpoints or tests used in DNT-studies. Forty-four DNT studies of BPA were identified from the open literature. Details about study design and results from each study, as well as the criteria for DNT testing according to the standardized OECD test guideline (TG) 426, were collected in a database. This enabled systematic and detailed comparisons between studies as well as to the criteria and recommendations stated in TG 426. Multivariate analyses were also used to investigate how different factors of the study design contributed to differences in study results. The analyses showed behavioral effects were often observed for endpoints that are not required according to OECD TG 426, such as anxiety-related, social and sexual behaviors, especially at very low doses and in female offspring. On the other hand relatively few studies observed any effects on motor activity, which is commonly used in screening for neurotoxic effects in regulatory testing. However, varied and to some extent seemingly contradictory results have been reported in these studies, especially for endpoints related to motor activity and anxiety and exploration. Many studies were also poorly reported, limiting these analyses. No strong conclusions could be drawn from the multivariate analyses. A few factors of study design, such as the size of the dose and number of dose levels used and the use of litter or individual pup as statistical unit seemed to have some influence on study results. In conclusion, this analysis suggests that DNT-studies conducted according to the standardized OECD TG 426 may overlook sensitive effects of BPA, and possibly other potential endocrine disruptors, especially in female offspring.
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| 11. |
- Hanberg, Annika
(författare)
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Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on vitamin A storage in rat hepatic stellate cells
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), popularly called dioxins, are persistent pollutants with widespread occurrence in the environment as well as in human food and tissues. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the most toxic dioxin, as well as other dioxin-like compounds induce a broad spectrum of biochemical and toxic effects, many of which occur at extremely low doses or concentrations. Thus, there is a great need for an appropriate human health risk assessment. However, due to several uncertainties, such as species differences in sensitivity and the great number of dioxin-like compounds, it is urgent that the mechanisms behind the toxic effects which are critical for human low-dose exposure are elucidated, i.e., effects on reproduction, fetal development, immune function, and tumour development. The essential nutrient vitamin A, which acts as a hormone, is needed for proper reproduction, development, immune function, and can also affect tumour development. In addition, TCDD and other dioxin-like compounds interfere with the vitamin A homeostasis. The interference of dioxin-like compounds with vitamin A homeostasis may thus explain part of their toxicity. An apparent effect of TCDD on vitamin A is a long-lasting inhibition of hepatic retinoid accumulation. The liver constitutes the major storage site for vitamin A in the body, but it also plays a central role in regulating retinoid homeostasis. The specific aim of the present study was to investigate possible mechanisms behind the inhibitory effect of TCDD on hepatic vitamin A accumulation in the rat. The results of the present study show that the TCDD-induced inhibition of vitamin A accumulation primarily occurs in the hepatic stellate cells which constitute the major storage site for vitamin A. A slow elimination of TCDD from hepatic cells is in accordance with the long-lasting inhibition of TCDD on the hepatic vitamin A accumulation. The impaired ability of stellate cells to accumulate vitamin A was neither caused by an effect of TCDD on the number of stellate cells nor was their phenotype altered by TCDD. In the stellate ce s, TCDD nearly completely abolished the activity of LRAT, the enzyme which catalyses the esterification of retinol to retinyl esters for storage. The decreased LRAT activity correlates well with the reduced accumulation of vitamin A (particularly retinyl esters) in these cells as well as in the liver as a whole. In the kidney, TCDD increased the LRAT activity, which can explain the increased renal retinyl ester levels. TCDD slightly decreased the intestinal uptake of retinol into Iymph, particularly during the initial phase of absorption. This decrease could also be explained by a corresponding decrease in the LRAT activity in the intestinal mucosa of TCDD-treated rats. In conclusion, the decreased LRAT activity in stellate cells is most probably a major contributing factor to the TCDD-induced inhibition of hepatic vitamin A accumulation. The lower uptake of vitamin A in the intestine of TCDD-treated rats, which also involves a slightly depressed LRAT activity, may also contribute to the decreased hepatic vitamin A levels. Thus, a common feature for the effects of TCDD on vitamin A metabolism observed in the present thesis is the tissue-specific alteration in the LRAT activity.
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| 12. |
- Hanberg, Annika, et al.
(författare)
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Phthalates and their metabolites in human breast milk, blood and urine as measures for monitoring exposure in human risk groups
- 2005
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- För att undersöka halter av ftalater i svenskar och vilken matris som bäst lämpar sig för hälsorelaterad miljöövervakning har ftalater och ftalatmetaboliter analyserats i en grupp kvinnor som nyligen fött barn. I samband med förlossning på Universitetssjukhuset i Lund tillfrågades förstföderskor om medverkan och 42 kvinnor kom att ingå i studien. När barnet var 2-3 veckor gammalt pumpade mamman ut 50 mL bröstmjölk. Blod- och urinprov togs en vecka senare. Omfattande förändringar av standardmetoder för provtagning av mjölk och blod gjordes för att minimera risken för kontaminering av proverna. För mjölkprovtagningen användes en specialkonstruerad manuell pump av polykarbonat med ftalatfri packning. Blodprov togs med hjälp av endast kanyl och provrör (eftersom propparna i vaccutainrör innehåller ftalater). Proverna förvarades i värmebehandlade glasbehållare och fosforsyra tillsattes för att motverka metabolism av ftalater i mjölk- och blodprover. Analyserna av bröstmjölk visade värden nära eller under detektionsgränsen (LOD) för flertalet ftalater eller deras metaboliter. Även i blod och serum var nivåerna vanligtvis nära eller under LOD. I urin analyserades endast metaboliter och dessa kunde kvantifieras i 53-100 % av proverna. Nivåerna av ftalatmetaboliter i urin hos de svenska kvinnorna var i paritet med nivåerna hos en allmänbefolkning i USA och Tyskland. Några klara korrelationer mellan nivåer i t ex urin och bröstmjölk respektive blod påvisades inte. Resultaten av studien anger att för närvarande är analys av ftalatmetaboliter i urin den mest framkomliga vägen för skattning av ftalatexponering hos människa. Provtagning och analys av mjölk och blod innebar betydligt större svårigheter. Framför allt framstår risken för kontaminering vid provtagning som betydande och en stor del av ftalaterna och dess metaboliter uppvisade låga halter, vid eller under LOD. Dessutom kan ftalater brytas ned i blod och mjölk. I flertalet internationella publicerade studier av ftalatexponering används urinmetabolit-analyser som ett mått på exponering för ftalater. I en nyligen publicerad amerikansk studie av ett 80-tal nyfödda pojkar sågs ett samband mellan kort ano-genitalt avstånd och nivåer av ftalatmetaboliter i urin hos deras mammor under graviditeten. Den amerikanska studien behöver bekräftas, men metaboliterna var desamma som i vår studie och en jämförelse visar att mediannivåerna var lägre för vissa men högre för andra metaboliter. Vår studie indikerar att svenska kvinnor i fertil ålder inte sällan exponeras för ftalater i nivåer som satts i samband med fosterpåverkan.
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| 13. |
- Hogberg, Johan, et al.
(författare)
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Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations
- 2008
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 116:3, s. 334-339
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Phthalates may pose a risk for perinatal developmental effects. An important question relates to the choice of suitable biological matrices for assessing exposure during this period. OBJECTIVES: This study was designed to measure the concentrations of phthalate diesters or their metabolites in breast milk, blood or serum, and urine and to evaluate their suitability for assessing perinatal exposure to phthalates. METHODS: In 2001, 2-3 weeks after delivery, 42 Swedish primipara provided breast milk, blood, and urine samples at home. Special care was taken to minimize contamination with phthalates (e.g., use of a special breast milk pump, heat treatment of glassware and needles, addition of phosphoric acid). RESULTS: Phthalate diesters and metabolites in milk and blood or serum, if detected, were present at concentrations close to the limit of detection. By contrast, most phthalate metabolites were detectable in urine at concentrations comparable to those from the general population in the United States and in Germany. No correlations existed between urine concentrations and those found in milk or blood/serum for single phthalate metabolites. Our data are at odds with a previous study documenting frequent detection and comparatively high concentrations of phthalate metabolites in Finnish and Danish mothers' milk. CONCLUSIONS: Concentrations of phthalate metabolites in urine are more informative than those in milk or serum. Furthermore, collection of milk or blood may be associated with discomfort and potential technical problems such as contamination (unless oxidative metabolites are measured). Although urine is a suitable matrix for health-related phthalate monitoring, urinary concentrations in nursing mothers cannot be used to estimate exposure to phthalates through milk ingestion by breast-fed infants.
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| 14. |
- Lignell, Sanna, et al.
(författare)
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Maternal body burdens of PCDD/Fs and PBDEs are associated with maternal serum levels of thyroid hormones in early pregnancy : a cross-sectional study
- 2016
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Ingår i: Environmental Health. - : Springer Science and Business Media LLC. - 1476-069X. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Thyroid hormones (THs) regulate many biological functions in the human body and are essential for normal brain development. Epidemiological studies have observed diverging associations between halogenated persistent organic pollutant (POP) exposure and concentrations of THs in pregnant women and their infants. We investigated whether background exposure to polybrominated diphenyl ethers (PBDEs) is related to TH status in a Swedish population of pregnant women and their infants. Furthermore, we examined associations between polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) and TH status in early pregnancy as an extension of an earlier study focusing on late pregnancy TH status. Methods: Free thyroxine (T4), total triiodo-thyronine (T3) and thyroid stimulating hormone (TSH) were analysed in serum from first-time mothers (N = 220-281) in the first and third trimester, and in infants (N = 115-150) 3 weeks and 3 months after delivery. Antibodies to thyroid peroxidase (anti-TPO) (N = 260) were measured in maternal third trimester serum. Maternal body burdens of PCBs (N = 281) were estimated from serum lipid PCB concentrations in late pregnancy, and PCDD/F (N = 97) and PBDE (N = 186) body burdens were estimated from concentrations in mother's milk lipids 3 weeks after delivery. Linear regression models allowed for covariate adjustment of the associations between ln-transformed POP body burdens and concentrations of TH and anti-TPO. Results: Maternal body burden of BDE-153 was inversely associated with first trimester total T3, otherwise no associations between PBDEs and first and second trimester THs were observed. No associations were found between maternal PBDE body burdens and infant THs. Maternal body burden of PCDD/Fs were inversely associated with first trimester total T3. No associations were observed between PCBs and first trimester THs. Third trimester anti-TPO was not associated with maternal PCBs, PCDD/Fs and PBDEs. Conclusions: Our results suggest that maternal PCDD/F and BDE-153 body burdens influence maternal TH status in early pregnancy, which is a critical period when maternal TH status influences fetal development.
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| 15. |
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| 16. |
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| 17. |
- Molander, Linda, et al.
(författare)
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Combining web-based tools for transparent evaluation of data for risk assessment : developmental effects of bisphenol A on the mammary gland as a case study
- 2017
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Ingår i: Journal of Applied Toxicology. - : Wiley. - 0260-437X .- 1099-1263. ; 37:3, s. 319-330
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Tidskriftsartikel (refereegranskat)abstract
- Different tools have been developed that facilitate systematic and transparent evaluation and handling of toxicity data in the risk assessment process. The present paper sets out to explore the combined use of two web-based tools for study evaluation and identification of reliable data relevant to health risk assessment. For this purpose, a case study was performed using in vivo toxicity studies investigating low-dose effects of bisphenol A on mammary gland development. The reliability of the mammary gland studies was evaluated using the Science in Risk Assessment and Policy (SciRAP) criteria for toxicity studies. The Health Assessment Workspace Collaborative (HAWC) was used for characterizing and visualizing the mammary gland data in terms of type of effects investigated and reported, and the distribution of these effects within the dose interval. It was then investigated whether there was any relationship between study reliability and the type of effects reported and/or their distribution in the dose interval. The combination of the SciRAP and HAWC tools allowed for transparent evaluation and visualization of the studies investigating developmental effects of BPA on the mammary gland. The use of these tools showed that there were no apparent differences in the type of effects and their distribution in the dose interval between the five studies assessed as most reliable and the whole data set. Combining the SciRAP and HAWC tools was found to be a useful approach for evaluating in vivo toxicity studies and identifying reliable and sensitive information relevant to regulatory risk assessment of chemicals. Copyright (c) 2016 John Wiley & Sons, Ltd. The present paper explores the combined use of the Science in Risk Assessment and Policy toxicity study evaluation method and the Health Assessment Workspace Collaborative tools for identification of reliable data relevant to health risk assessment. Combining the Science in Risk Assessment and Policy and Health Assessment Workspace Collaborative tools was found to be a useful and transparent approach for evaluating in vivo toxicity studies and identifying reliable and sensitive information relevant to regulatory risk assessment of chemicals.
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| 18. |
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| 19. |
- Molander, Linda, 1984-, et al.
(författare)
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Low dose effects of bisphenol A on the developing mammary gland - Combining new web-based tools to identify reliable and relevant data for regulatory risk assessment
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Effects on the developing mammary gland have been repeatedly investigated and reported for bisphenol A (BPA) in experimental animals at doses close to or within human exposure range, and highlighted as being of potential concern to human health.Objective: The present study provides a characterization of in vivo effects of BPA on the developing mammary gland in relation to the temporary tolerable daily intake (t-TDI), recently established by EFSA. The mammary gland data set was also used to explore the combined use of two different web-based tools for identifying sensitive and reliable data for risk assessment purposes.Methods: The Health Assessment Workspace Collaborative (HAWC) was used for characterizing the mammary gland data in terms of type of effects investigated and reported and the distribution of these effects within the low dose range. The reliability of the mammary gland studies was evaluated using the Science in Risk Assessment and Policy (SciRAP) criteria. The results from HAWC and SciRAP were then combined to investigate whether there would be a shift in the type of effects reported and/or their distribution in the dose interval when considering only the studies judged as most reliable.Results: No clear relationship could be identified between the reliability of the studies as assessed according to the SciRAP criteria and the type of mammary gland effects reported or their distribution within the low dose range, respectively.Conclusions: The combined use of the HAWC and SciRAP tools would comprise a useful methodology for identifying reliable and sensitive information from in vivo toxicity studies of relevance to consider in the regulatory risk assessment process.
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| 20. |
- Molander, Linda, et al.
(författare)
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Science in Risk Assessment and Policy (SciRAP) : An Online Resource for Evaluating and Reporting In Vivo (Eco)Toxicity Studies
- 2015
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Ingår i: Human and Ecological Risk Assessment. - : Informa UK Limited. - 1080-7039 .- 1549-7860. ; 21:3, s. 753-762
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Tidskriftsartikel (refereegranskat)abstract
- (Eco)toxicity studies conducted according to internationally standardized test guidelines are often considered reliable by default and preferred as key evidence in regulatory risk assessment. At the same time regulatory agencies emphasize the use of all relevant (eco)toxicity data in the risk assessment process, including non-standard studies. However, there is a need to facilitate the use of such studies in regulatory risk assessment. Therefore, we propose a framework that facilitates a systematic and transparent evaluation of the reliability and relevance of (eco)toxicity in vivo studies for health and environmental risk assessment. The framework includes specific criteria to guide study evaluation, as well as a color-coding tool developed to aid the application of these criteria. In addition we provide guidance intended for researchers on how to report non-standard studies to ensure that they meet regulatory requirements. The intention of the evaluating and reporting criteria is to increase the usability of all relevant data that may fill information gaps in chemical risk assessments. The framework is publically available online, free of charge, at the Science in Risk Assessment and Policy (SciRAP) website: [GRAPHICS] . The aim of this article is to present the framework and resources available at the SciRAP website.
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| 21. |
- Van den Berg, Martin, et al.
(författare)
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The 2005 World Health Organization reevaluation of human and mammalian toxic equivalency factors for dioxins and dioxin-like compounds
- 2006
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Ingår i: Toxicological Sciences. - : Oxford University Press. - 1096-6080 .- 1096-0929. ; 93:2, s. 223-241
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Tidskriftsartikel (refereegranskat)abstract
- In June 2005, a World Health Organization (WHO)-International Programme on Chemical Safety expert meeting was held in Geneva during which the toxic equivalency factors (TEFs) for dioxin-like compounds, including some polychlorinated biphenyls (PCBs), were reevaluated. For this reevaluation process, the refined TEF database recently published by Haws et al. (2006, Toxicol. Sci. 89, 4-30) was used as a starting point. Decisions about a TEF value were made based on a combination of unweighted relative effect potency (REP) distributions from this database, expert judgment, and point estimates. Previous TEFs were assigned in increments of 0.01, 0.05, 0.1, etc., but for this reevaluation, it was decided to use half order of magnitude increments on a logarithmic scale of 0.03, 0.1, 0.3, etc. Changes were decided by the expert panel for 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) (TEF = 0.3), 1,2,3,7,8-pentachlorodibenzofuran (PeCDF) (TEF = 0.03), octachlorodibenzo-p-dioxin and octachlorodibenzofuran (TEFs = 0.0003), 3,4,4',5-tetrachlorbiphenyl (PCB 81) (TEF = 0.0003), 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) (TEF = 0.03), and a single TEF value (0.00003) for all relevant mono-ortho-substituted PCBs. Additivity, an important prerequisite of the TEF concept was again confirmed by results from recent in vivo mixture studies. Some experimental evidence shows that non-dioxin-like aryl hydrocarbon receptor agonists/antagonists are able to impact the overall toxic potency of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds, and this needs to be investigated further. Certain individual and groups of compounds were identified for possible future inclusion in the TEF concept, including 3,4,4'-TCB (PCB 37), polybrominated dibenzo-p-dioxins and dibenzofurans, mixed polyhalogenated dibenzo-p-dioxins and dibenzofurans, polyhalogenated naphthalenes, and polybrominated biphenyls. Concern was expressed about direct application of the TEF/total toxic equivalency (TEQ) approach to abiotic matrices, such as soil, sediment, etc., for direct application in human risk assessment. This is problematic as the present TEF scheme and TEQ methodology are primarily intended for estimating exposure and risks via oral ingestion (e.g., by dietary intake). A number of future approaches to determine alternative or additional TEFs were also identified. These included the use of a probabilistic methodology to determine TEFs that better describe the associated levels of uncertainty and "systemic" TEFs for blood and adipose tissue and TEQ for body burden.
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| 22. |
- Wejheden, Carolina, et al.
(författare)
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Osteopontin : a rapid and sensitive response to dioxin exposure in the osteoblastic cell line UMR-106
- 2006
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 341:1, s. 116-120
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Tidskriftsartikel (refereegranskat)abstract
- 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disrupting environmental pollutant that, among other effects, affects bone tissue. TCDD modulates the transcription of various genes, e.g., CYP1A1, and the present study is a part of a project aiming at developing an in vitro model system for identifying biomarkers specific for dioxin-induced effects in osteoblasts. Osteopontin (OPN) is an adhesion protein, suggested to be important in bone remodeling and our results indicate that TCDD down-regulates the transcription of OPN in the osteoblastic cell line, UMR-106. The present study shows that UMR-106 expresses the AhR and that the expression of CYP1A1 is induced after exposure to TCDD, while down-regulation of OPN is an even more rapid response and a sensitive biomarker to TCDD exposure in this osteoblastic cell line. In conclusion, this osteoblastic cell line may be used as an in vitro model-system for studying dioxin-induced effects on osteoblasts.
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| 23. |
- Wejheden, Carolina, et al.
(författare)
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Transgenic mice with a constitutively active aryl hydrocarbon receptor (CA-AhR) display a gender specific bone phenotype
- 2010
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 114:1, s. 48-58
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Tidskriftsartikel (refereegranskat)abstract
- Bone tissue homeostasis is governed by hormones, growth factors and cytokines and can be distorted by environmental pollutants such as ligands to the aryl hydrocarbon receptor (AhR). A transgenic mouse expressing a constitutively active AhR (CA-AhR), mimicking continuous low-dose exposure to AhR-ligands, was used to explore potential long-term effects of these ligands on bone The density, content and dimensions of cortical and trabecular bone, as well as physical properties, were significantly altered in female transgenic mice, while almost no alterations were detected in males. Osteoclast volume density and serum level of CTX, reflecting osteoclast activity, were both increased by approximately 60% in female CA-AhR mice, while serum TRAP 5b, reflecting osteoclast numbers, was unchanged. Subsequently, the resorption index (CTX/TRAP 5b) was increased by 90% indicating increased osteoclast activity in female CA-AhR. Moreover, the protein level of the osteoclast collagenase cathepsin K was increased by 40 % in bone extracts of female CA-AhR mice. The mRNA expression of several osteoclast and osteoblast associated genes were altered in female transgenic mice, but not in males. Notably, early markers for osteoclast and osteoblast differentiation were normal, while the expression of functional markers of osteoclasts and osteoblasts were reduced. In conclusion, a low continuous activation of the AhR leads to a skeletal phenotype with increased bone resorption associated with more ductile bones in females but not in males. The results indicate the presence of an interaction between the AhR and a female specific mechanism implicated in inhibition of osteoclast development and function. Female bone tissue appears more susceptible to dioxins and other AhR-ligands than male bone tissue.
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| 24. |
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| 25. |
- Ågerstrand, Marlene, et al.
(författare)
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A call for action : Improve reporting of research studies to increase the scientific basis for regulatory decision-making
- 2018
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Ingår i: Journal of Applied Toxicology. - : Wiley. - 0260-437X .- 1099-1263. ; 38:5, s. 783-785
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Tidskriftsartikel (refereegranskat)abstract
- This is a call for action to scientific journals to introduce reporting requirements for toxicity and ecotoxicity studies. Such reporting requirements will support the use of peer-reviewed research studies in regulatory decision-making. Moreover, this could improve the reliability and reproducibility of published studies in general and make better use of the resources spent in research.
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| 26. |
- Öberg, Mattias, et al.
(författare)
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Toxicity of Bromkal 70-5DE, a technical mixture of polybrominated diphenyl ethers, following 28 d of oral exposure in rats and impact of analysed impurities
- 2010
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 80:2, s. 137-143
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Tidskriftsartikel (refereegranskat)abstract
- The subacute toxicity of a commercial polybrominated diphenyl ether (PBDE) preparation, Bromkal 70-5DE, was investigated. In addition to a vehicle control, the mixture was given orally to male and female Sprague-Dawley rats for 28d at three dose levels; 2.5, 25 and 250mgkg(-1) b.w.d(-1). The observed effects include increased hepatic EROD activity (from 2.5mgkg(-1)d(-1)); increased liver weight (males), increased PROD activity and depletion of hepatic retinoids (from 25mgkg(-1)d(-1)); and increased liver weight (females), marked histological changes in the liver and lungs, as well as increased serum parameters such as total protein, cholesterol and albumin (from 250mgkg(-1)d(-1)). Chemical analysis of the PBDE mixture with gas chromatography/mass spectrometry (GS/MS) showed impurities of polybrominated dibenzofurans and to a lesser extent dibenzodioxins, in total levels of about 7.0mugg(-1) of Bromkal technical mixture. The animals were thereby exposed to an estimated dose of dioxin-like equivalents corresponding to 1.3-131ng TEQkg(-1) b.w.d(-1). It cannot be ruled out that this level of impurities can explain the hepatic EROD induction and hepatic retinoid depletion, which are considered typical markers of toxicity mediated via the aryl hydrocarbon receptor (AhR).
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