| 1. |
- Amzal, Billy, et al.
(författare)
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Population Toxicokinetic Modeling of Cadmium for Health Risk Assessment
- 2009
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Ingår i: Journal of Environmental Health Perspectives. - : US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE. - 0091-6765 .- 1552-9924. ; 117:8, s. 1293-1301
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cadmium is a widespread environmental pollutant that has been shown to exert toxic effects on kidney and bones in humans after long-term exposure. Urinary cadmium concentration is considered a good biomarker of accumulated cadmium in kidney, and diet is the main source of cadmium among nonsmokers. OBJECTIVE: Modeling the link between urinary cadmium and dietary cadmium intake is a key step in the risk assessment of long-term cadmium exposure. There is, however, little knowledge on how this link may vary, especially for susceptible population strata. METHODS: We used a large population-based study (the Swedish Mammography Cohort), with repeated dietary intake data covering a period of 20 years, to compare estimated dietary cadmium intake with urinary cadmium concentrations on an individual basis. A modified version of the Nordberg-Kjellstrom model and a one-compartment model were evaluated in terms of their predictions of urinary cadmium. We integrated the models and quantified the between-person variability of cadmium half-life in the population. Finally, sensitivity analyses and Monte Carlo simulations were performed to illustrate how the latter model could serve as a robust tool supporting the risk assessment of cadmium in humans. RESULTS: The one-compartment population model appeared to be an adequate modeling option to link cadmium intake to urinary cadmium and to describe the population variability. We estimated the cadmium half-life to be about 11.6 years, with about 25% population variability. CONCLUSIONS: Population toxicokinetic models can be robust and useful tools for risk assessment of chemicals, because they allow quantification and integration of population variability in toxicokinetics.
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| 2. |
- Ernstgård, Lena, et al.
(författare)
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Acute Effects of Some Volatile Organic Compounds Emitted From Waters-Based Paints
- 2007
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Ingår i: Journal of Occupational and Environmental Medicine. - 1076-2752 .- 1536-5948. ; 49:8, s. 880-889
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Acute effects during controlled exposure to some of the volatile organic compounds emitted from water-based paints were evaluated. METHODS: Healthy volunteers (10 atopics, 10 nonatopics, and 10 painters) were exposed to a mixture of propyleneglycol, texanol, diethyleneglycol monoethylether, diethyleneglycol monobutyl ether, and dipropyleneglycol monomethyl ether at a total concentration of 35 mg/m3 (G), a mixture of G and ammonia (15 mg/m3) (GA), and clean air (C). RESULTS: Subjective ratings of irritation in eyes, nose, throat, and dyspnea were significantly higher during the G and GA conditions, when compared with during the C condition. Nasal mucosal swelling was observed after G but not after GA exposure. No effects of the exposure on the pulmonary function, markers of inflammation in nasal lavages, and renal function in urine were seen. CONCLUSION: Exposure to G and GA caused mild irritation in eyes, nose, and airways.
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| 3. |
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| 4. |
- Ganguly, Koustav, et al.
(författare)
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Computational modeling of lung deposition of inhaled particles in chronic obstructive pulmonary disease (COPD) patients : identification of gaps in knowledge and data
- 2019
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Ingår i: Critical reviews in toxicology. - : TAYLOR & FRANCIS LTD. - 1040-8444 .- 1547-6898. ; 49:2, s. 160-173
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Forskningsöversikt (refereegranskat)abstract
- Computational modeling together with experimental data are essential to assess the risk for particulate matter mediated lung toxicity and to predict the efficacy, safety and fate of aerosolized drug molecules used in inhalation therapy. In silico models are widely used to understand the deposition, distribution, and clearance of inhaled particles and aerosols in the human lung. Exacerbations of chronic obstructive pulmonary disease (COPD) have been reported due to increased particulate matter related air pollution episodes. Considering the profound functional, anatomical and structural changes occurring in COPD lungs, the relevance of the existing in silico models for mimicking diseased lungs warrants reevaluation. Currently available computational modeling tools were developed for the healthy adult (male) lung. Here, we analyze the major alterations occurring in the airway structure, anatomy and pulmonary function in the COPD lung, as compared to the healthy lung. We also scrutinize the various physiological and particle characteristics that influence particle deposition, distribution and clearance in the lung. The aim of this review is to evaluate the availability of the fundamental knowledge and data required for modeling particle deposition in a COPD lung departing from the existing healthy lung models. The extent to which COPD pathophysiology may affect aerosol deposition depends on the relative contribution of several factors such as altered lung structure and function, bronchoconstriction, emphysema, loss of elastic recoil, altered breathing pattern and altered liquid volumes that warrant consideration while developing physiologically relevant in silico models.
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| 5. |
- Glynn, Anders, et al.
(författare)
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PFAS i blod – modellering av exponering via dricksvatten
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med projektet var att undersöka sambandet mellan halter av per- och polyfluorerade alkylsubstanser (PFAS) i dricksvatten (DV) och i serumprover från befolkningsgrupper som druckit PFAS-förorenat DV under lång tid. Målet var att utveckla en populationsmodell där PFAS-halter i serum kan uppskattas från PFAS-halter i DV och exponeringstid för detta DV. I projektet användes redan publicerade resultat från studier av PFAS-halter i serum och DV, omfattande anställda vid Arvidsjaurs flygplats (brunnsvatten), permanent/fritidsboende i närheten av Luleå flygplats (brunnsvatten), permanent/fritidsboende i närheten av Visby flygplats (brunnsvatten), och invånare från Uppsala (kommunalt DV). En grupp vuxna från Karlshamn (kommunalt vatten) fick representera populationer som druckit rent DV. Linjära regressionsanalyser visade starka samband mellan uppmätta PFAS-halter i serum och DV. PFHxS uppvisade den högsta kvoten mellan halt i serum och DV (ca 100), medan PFHxA och PFBS hade kvoter i intervallet 1-2. Skillnaderna i kvoter, som illustrerar hur effektivt PFAS bioackumuleras i kroppen från DV, är relaterad till hur länge olika PFAS stannar i kroppen efter avslutad exponering (halveringstider). PFAS med långa halveringstider (PFOA, PFHxS, PFOS) hade klart högre kvoter, och därmed högre bioackumulering, än PFAS med korta halveringstider (PFHxA, PFBS). I separata regressionsanalyser observerades lägre kvoter mellan PFAS-halt i serum och DV hos kvinnor än hos män, vilket antyder att kvinnor inte bioackumulerar de studerade PFAS från DV i lika hög grad som män. Befolkningen i Sverige exponeras för PFAS från andra källor än DV, vilket leder till bakgrundshalter av PFAS i serum även bland dem som inte druckit förorenat DV. Resultaten från regressionsanalyserna användes för att uppskatta vid vilka halter av PFAS i DV som det med stor sannolikhet går att upptäcka PFAS-halter i serum som ligger över bakgrundshalterna. Dessa PFAS-halter i DV varierade mellan olika PFAS, från ca 50 ng/L för PFOA till ca 100 ng/L för PFOS. Dessa halter ligger mycket högre än de som normalt uppmäts i kommunalt och enskilt DV i Sverige, och representerar halter i starkt förorenade områden. Med den relativt enkla populationsmodell som utvecklats i projektet kan man beräkna hur halterna av PFAS i serum påverkas av PFAS-halterna i DV. Dessutom kan man beräkna hur PFAS-halterna i serum påverkas av exponeringstiden för det förorenade DV, samt hur halterna minskar i serum efter övergång till rent DV. Som ingångsvärden i modellen användes de bakgrundshalter av PFAS i serum och kvoter mellan serum/DV-halter av PFAS som tagits fram i regressionsanalysen. Dessutom utnyttjades de halveringstider som tagits fram för de som arbetade (och konsumerade PFAS-förorenat DV) vid Luleå flygplats, samt en population vuxna från Canada. I ett test av modellen jämfördes de modellerade halterna av PFOA, PFHxS och PFOS i serum med uppmätta halter i tre populationer från Sverige (Ronneby), Italien (Veneto) och Arnsberg (Tyskland) som druckit förorenat DV under lång tid. Jämförelsen visade att modellen på ett bra sätt uppskattar variationen av halterna i serum i populationen, men att den underskattar medelhalterna, om medianen används vid jämförelsen. Om de modellerade medelvärdena (artimetiskt medelvärde) istället används i jämförelsen med de uppmätta medianerna, ligger de modellerade och uppmätta medel-halterna nära varandra. De observerade skillnaderna kan bero på att den regressionsanalys som användes för att ta fram ingångsvärdena i modellen påverkat fördelningen av värdena på ett sätt som inte helt överensstämmer med fördelningen i de studerade populationerna. Eliminering av PFAS efter övergång till rent DV modellerades också. Som exempel användes haltdata från de Ronnebybor som druckit förorenat DV under lång tid. Som slutpunkt i modelleringen användes den serumhalt som i medeltal representerar ett långsiktigt intag av PFAS i nivå med det tolerabla veckointaget (serumTVI), som EFSA tagit fram i sin senaste riskbedömning. SerumTVI är uppskattat för en summa-halt av PFOA, PFNA, PFHxS och PFOS i serum (6,9 ng PFAS4/ml). Modelleringen pekar mot en stor variation i den tid det tar innan serumTVI nås i en befolkningsgrupp efter byte till rent DV. Den kortaste tiden modellerades till 14 år och den längsta till längre än en livstid. Resultaten i projektet uppmuntrar till fortsatt utveckling av modellen för uppskattning av PFAS-halter i serum från uppmätta halter i DV.
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| 13. |
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| 14. |
- Johanson, Jan, et al.
(författare)
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Interorganizational relations in industrial systems : a network approach compared with the transaction cost approach
- 1987
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- A network approach, as it is developed by some Swedish researchers inindustrial marketing and international business (see e.g. Hägg &Johanson (ed.), 1982 and Hammarkvist, Håkansson & Mattsson, 1982) iscompared with the transaction cost approach associated with OliverWilliamson (e.g. Williamson, 1975, 1979, 1981). The reason we makesuch a comparison is that we often get questions from colleagues inthe scientific community, suggesting that what we try to do is rathersimilar to what the transaction cost approach is doing.
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| 15. |
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| 18. |
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| 19. |
- Johanson, Per, 1963, et al.
(författare)
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Prognostic value of ST-segment resolution-when and what to measure.
- 2003
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Ingår i: European heart journal. - 0195-668X. ; 24:4, s. 337-45
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of ST-segment resolution during acute myocardial infarction has, during recent years, challenged coronary angiography as gold-standard for predicting myocardial reflow and future risk. We have previously reported that continuous ST-monitoring can be done accurately in the clinical setting. We now set out to compare the prognostic value of previously suggested cut-offs for ST-segment resolution, and determine the times to measure these.
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| 20. |
- Johansson, Mia K. V., et al.
(författare)
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Does industry take the susceptible subpopulation of asthmatic individuals into consideration when setting derived no-effect levels?
- 2016
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Ingår i: Journal of Applied Toxicology. - : John Wiley & Sons. - 0260-437X .- 1099-1263. ; 36:11, s. 1379-1391
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Tidskriftsartikel (refereegranskat)abstract
- Asthma, a chronic respiratory disease, can be aggravated by exposure to certain chemical irritants. The objectives were first to investigate the extent to which experimental observations on asthmatic subjects are taken into consideration in connection with the registration process under the EU REACH regulation, and second, to determine whether asthmatics are provided adequate protection by the derived no-effect levels (DNELs) for acute inhalation exposure. We identified substances for which experimental data on the pulmonary functions of asthmatics exposed to chemicals under controlled conditions are available. The effect concentrations were then compared with DNELs and other guideline and limit values. As of April 2015, only 2.6% of 269 classified irritants had available experimental data on asthmatics. Fourteen of the 22 identified substances with available data were fully registered under REACH and we retrieved 114 reliable studies related to these. Sixty-three of these studies, involving nine of the 14 substances, were cited by the REACH registrants. However, only 17 of the 114 studies, involving four substances, were regarded as key studies. Furthermore, many of the DNELs for acute inhalation were higher than estimated effect levels for asthmatics, i.e., lowest observed adverse effect concentrations or no-observed adverse effect concentrations, indicating low or no safety margin. We conclude that REACH registrants tend to disregard findings on asthmatics when deriving these DNELs. In addition, we found examples of DNELs, particularly among those derived for workers, which likely do not provide adequate protection for asthmatics. Copyright (c) 2016 The Authors Journal of Applied Toxicology Published by John Wiley & Sons Ltd. We investigate the extent to which experimental observations on asthmatic subjects are taken into consideration by REACH registrants and determine whether asthmatics are provided adequate protection by the acute inhalation Derived No-Effect Levels. Of 114 studies concerning 14 substances fulfilling our inclusion criteria, 63 studies, involving nine substances, were cited by the REACH registrants. However, only 17 of the 114 studies, involving four substances, were regarded as key studies. Furthermore, many of the Derived No-Effect Levels were higher than Lowest- or No-Observed Adverse Effect Concentrations values from these studies.
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| 25. |
- Juran, Stephanie A, et al.
(författare)
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Odor thresholds for 2,4,6 -trichloroanisole reviewed in the context of indoor air quality
- 2015
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Ingår i: Proceedings - Healthy Buildings 2015 America: Innovation in a Time of Energy Uncertainty and Climate Adaptation, HB 2015. - : International Society of Indoor Air Quality and Climate. - 9781510821286 ; , s. 415-418
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Konferensbidrag (refereegranskat)abstract
- Chloroanisoles have received minimal attention in research on indoor air quality (IAQ) although they can affect comfort and maybe also health when levels are sufficiently high to evoke malodor. Here, we review the literature for odor thresholds (OT) for 2,4,6-trichloroanisole to estimate at which concentrations air is perceived as malodorous, and discuss the caveats in measuring and comparing OTs. In general, reported OTs for 2,4,6-trichloroanisole are extremely low but still in the range measured in indoor air of problem buildings, as we reported recently (Lorentzen et. al., 2015). However, OTs vary considerably due to methodological constraints such as different methods of stimulus presentation. Only one study (not published in a peer reviewed journal) reports OTs in air, and the data suggest that 2,4,6-trichloroanisole can be among the most potent microbial odors. Additional studies are therefore warranted. It will also be important in future studies to investigate the perceived odor quality of CAs in the context of IAQ problems with dampness and mold.
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| 26. |
- Liljedahl, Emelie Rietz, et al.
(författare)
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Filaggrin polymorphisms and the uptake of chemicals through the skin—a human experimental study
- 2021
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Ingår i: Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 129:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The filaggrin protein is important for skin barrier structure and function. Loss-of-function (null) mutations in the filaggrin gene FLG may increase dermal absorption of chemicals. OBJECTIVE: The objective of the study was to clarify if dermal absorption of chemicals differs depending on FLG genotype. METHOD: We performed a quantitative real-time polymerase chain reaction (qPCR)-based genetic screen for loss-of-function mutations (FLG null) in 432 volunteers from the general population in southern Sweden and identified 28 FLG null carriers. In a dermal exposure experiment, we exposed 23 FLG null and 31 wild-type (wt) carriers to three organic compounds common in the environment: the polycyclic aromatic hydrocarbon pyrene, the pesticide pyrimethanil, and the ultraviolet-light absorber oxybenzone. We then used liquid-chromatography mass-spectrometry to measure the concentrations of these chemicals or their metabolites in the subjects’ urine over 48 h following exposure. Furthermore, we used long-range PCR to measure FLG repeat copy number variants (CNV), and we performed population toxicokinetic analysis. RESULTS: Lag times for the uptake and dermal absorption rate of the chemicals differed significantly between FLG null and wt carriers with low (20–22 repeats) and high FLG CNV (23–24 repeats). We found a dose-dependent effect on chemical absorption with increasing lag times by increasing CNV for both pyrimethanil and pyrene, and decreasing area under the urinary excretion rate curve (AUCð0–40hÞ ) with increasing CNV for pyrimethanil. FLG null carriers excreted 18% and 110% more metabolite (estimated by AUCð0–40hÞ ) for pyrimethanil than wt carriers with low and high CNV, respectively. CONCLUSION: We conclude that FLG genotype influences the dermal absorption of some common chemicals. Overall, FLG null carriers were the most susceptible, with the shortest lag time and highest rate constants for skin absorption, and higher fractions of the applied dose excreted. Furthermore, our results indicate that low FLG CNV resulted in increased dermal absorption of chemicals. https://doi.org/10.1289/EHP7310.
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| 27. |
- Lorentzen, Johnny C., et al.
(författare)
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Evidence of Unrecognized Indoor Exposure to Toxic Chlorophenols and Odorous Chloroanisoles in Denmark, Finland, and Norway
- 2023
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Ingår i: Indoor Air. - 0905-6947. ; 2023
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Tidskriftsartikel (refereegranskat)abstract
- Production and use of chlorophenols (CPs) are being phased out around the globe, but with considerable lag in some highlypopulated countries. The process could be incentivized by leading countries sharing their experiences on problems thatoccurred, including the built environment. We previously reported that Swedish industry and authorities promoted CPs,including pentachlorophenol (PCP), as wood preservatives in buildings for decades. Yet, Swedish indoor research did notrecognize exposure to the hazardous CPs and their odor potent derivatives, the chloroanisoles (CAs), which smell like moldand still evolve from legacy preservatives in damp building structures. We hypothesized that the toxic CPs and odorous CAscould be key players for health and odor problems not only in Sweden but also in the neighboring Nordic countries. We foundno reports in scientific medical literature of CPs being used in buildings in these countries. However, grey literature shows thatCPs were indeed used, even during building booms, in house exteriors, constructions, and interiors, from the 1950s up to thelate 1970s (Denmark) and even the 1990s (Finland and Norway). One application of CPs was in houses erected on dampness-prone house foundations, conditions ideal for formation of odorous CAs through microbial methylation. Furthermore, oursearches suggest that these problematic chemicals played hitherto unrecognized key roles when indoor air research evolved.Thus, odor became an important aspect of the “sick building syndrome” in Denmark and an early warning sign of health risksin Finland, as asthma and allergy were attributed to “dampness and mold.” None of the countries addressed the possible linksbetween odor and health effects and exposure to CAs and CPs. In conclusion, our results suggest that unrecognized indoorexposure to toxic CPs and odorous CAs has mislead Nordic indoor air research for decades.
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| 28. |
- Lorentzen, Johnny C., et al.
(författare)
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Mold Odor from Wood Treated with Chlorophenols despite Mold Growth That Can Only Be Seen Using a Microscope
- 2024
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Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- We previously reported that indoor odorous chloroanisoles (CAs) are still being emitted due to microbial methylation of hazardous chlorophenols (CPs) present in legacy wood preservatives. Meanwhile, Swedish researchers reported that this malodor, described since the early 1970s, is caused by hazardous mold. Here, we examined to what extent CP-treated wood contains mold and if mold correlates with perceived odor. We found no studies in PubMed or Web of Science addressing this question. Further, we investigated two schools built in the 1960s with odor originating from crawlspaces. No visible mold was evident in the crawlspaces or on the surfaces of treated wood samples. Using a microscope, varying amounts of mold growth were detected on the samples, all containing both CP(s) and CA(s). Some samples smelled, and the odor correlated with the amount of mold growth. We conclude that superficial microscopic mold on treated wood suffices produced the odor. Further, we argue that CPs rather than mold could explain the health effects reported in epidemiological studies that use mold odor as an indicator of hazardous exposure.
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| 29. |
- Lorentzen, Johnny, et al.
(författare)
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Overcrowding and Hazardous Dwelling Condition Characteristics : A Systematic Search and Scoping Review of Relevance for Health
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 19:23
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Tidskriftsartikel (refereegranskat)abstract
- Crowding in dwellings is an important public health issue. We hypothesize that overcrowding may cause indirect health effects by adversely affecting the dwelling itself, for example, by increasing dampness leading to mold. We therefore performed a systematic search and a scoping review on overcrowding leading to dwelling condition characteristics of relevance for health. A literature search was performed using the PubMed and Scopus databases up to 5 March 2021. The search yielded 100 records with relevant information. We found that overcrowding is defined in numerous ways and often address “socially deprived” populations. Six studies report associations of overcrowding with at least one dwelling condition characteristic, namely lead, cadmium, microorganism distribution, dust mite and cockroach allergens in dust, cockroach infestation, peeling paint, and mold. One of the studies reports associations between several characteristics, e.g., association of mold with cleanliness and rodent infestation, and points out the common use of pesticides. Additional characteristics were extracted from the remaining 94 records, without data on statistical associations with overcrowding. Our review suggests that multiple potentially hazardous dwelling condition characteristics often coincide in overcrowded dwellings. The epidemiological attribution of health effects to any characteristic is therefore difficult. Causal relationships are even more difficult to establish, as overcrowding is also associated with a range of social and other circumstances that may affect health. The complexity should be considered by scientists and practitioners dealing with overcrowding in dwellings. © 2022 by the authors.
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| 30. |
- Mattsson, Lars-Gunnar, et al.
(författare)
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Discovering market networks
- 2006
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Ingår i: European Journal of Marketing. - 0309-0566. ; 40:3/4, s. 259-274
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Tidskriftsartikel (refereegranskat)
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| 31. |
- Mattsson, Lars-Gunnar, et al.
(författare)
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Internationalisation in Industrial Systems - a Network Approach
- 2015. - 1st
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Ingår i: Knowledge, Networks and Power: The Uppsala School of International Business. - London : Palgrave Macmillan. - 9781137508829 - 9781137508805 ; , s. 111-132
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 32. |
- Nihlén, Annsofi, et al.
(författare)
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Experimental exposure to methyl teriary-butyl ether : II. Acute effects in humans
- 1998
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X .- 1096-0333. ; 148:2, s. 281-287
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Tidskriftsartikel (refereegranskat)abstract
- Methyl tertiary-butyl ether (MTBE) is widely used in gasoline as an oxygenate and octane enhancer. Acute effects, such as headache, nausea, and nasal and ocular irritation, have been associated with the exposure to gasoline containing MTBE. The aim of this study was to assess acute health effects up to the Swedish occupational exposure limit value, both with objective methods and a questionnaire. Ten healthy male volunteers were exposed to MTBE vapor for 2 h at three levels (5, 25, and 50 ppm), during light physical work (50 W). All subjects rated the degree of irritative symptoms, discomfort, and CNS effects before, during, and after all three exposure occasions using a questionnaire. Answers were given on a 100-mm visual analog scale, graded from "not at all" to "almost unbearable." Ocular (redness, tear film break-up time, self-reported tear film break-up time, conjunctival epithelial damage, and blinking frequency) and nasal (mouth and nasal peak expiratory flow, acoustic rhinometry, biochemical inflammatory markers, and cells in nasal lavage) measurements were performed mainly at the highest exposure level. The ratings of solvent smell increased dramatically (ratings up to 50% of the scale) as the volunteers entered the chamber and declined slowly with time (p < 0.05, repeated-measures ANOVA). All other questions were rated from "not at all" to "hardly at all" (0-10% of the scale) with no significant relation to exposure. The eye measurements showed no effects of MTBE exposure. Blockage index, a measure of nasal airway resistance calculated from the peak expiratory flows, increased significantly after exposure; however, the effect was not related to exposure level. In addition, a nonsignificant tendency of decreased nasal volume was seen in the acoustic rhinometry measurements, but with no clear dose-effect relationship. In conclusion, our study suggests no or minimal acute effects of MTBE vapor upon short-term exposure at relatively high levels.
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| 33. |
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| 34. |
- Nyström-Kandola, Jennifer, et al.
(författare)
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Delrapport 1. Överföring av perfluoroalkylsyror från foder och dricksvatten till livsmedelsproducerande djur, och till livsmedel från dessa djur
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med denna rapport är att redovisa beräkningar av överföring av PFAS från dricksvatten och foder till livsmedelsproducerande djur och vidare till mjölk, kött, köttbiprodukter (lever) och ägg. Beräkningarna fokuserar på PFOA, PFNA, PFHxS och PFOS (PFAS4) och baseras främst på data från experimentella studier där livsmedelsproducerande djur på kontrollerat sätt exponerats för höga PFAS-halter från foder/dricksvatten. I beräkningarna uppskattades nivån av PFAS4-halter i foder och vatten som innebär att PFAS4-halter i de animaliska livsmedlen når upp till nivåer som motsvarar EUs gränsvärden eller åtgärdsgränser för PFAS4 i animaliska livsmedel (maxhalter). Förutom de ovan nämnda beräkningarna av maxhalter i foder och vatten, illustreras olika tillvägagångssätt för att göra beräkningar som kan vara till hjälp vid riskbedömning och riskhantering av PFAS i primärproduktionen av animaliska livsmedel. Resultaten av beräkningarna i föreliggande rapport får ses som ungefärliga eftersom det finns få publicerade studier inom området. Detta gör att ingångsdata i beräkningarna är osäkra. Dessutom har den biologiska variationen i ingångsdata inte beaktats. Resultaten ger dock en fingervisning om vilka animaliska produktionssystem som vid PFAS förorening av djurens foder/dricksvatten löper störst risk överskrida EUs gränsvärdes- och åtgärdsgränsnivåer för PFAS4. Data för beräkningarna hittades för mjölkko (mjölk, kött, lever), köttdjur (nöt, kött, lever), gris (kött), värphöns (ägg), slaktkyckling (kött, lever) och får (kött, lever).
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| 35. |
- Nyström-Kandola, Jennifer, et al.
(författare)
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Low concentrations of perfluoroalkyl acids (PFAAs) in municipal drinking water associated with serum PFAA concentrations in Swedish adolescents
- 2023
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Ingår i: Environment International. - 0160-4120 .- 1873-6750. ; 180
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Tidskriftsartikel (refereegranskat)abstract
- While highly contaminated drinking water (DW) is a major source of exposure to perfluoroalkyl acids (PFAAs), the contribution of low-level contaminated DW (i.e. < 10 ng/L of individual PFAAs) to PFAA body burdens has rarely been studied. To address this knowledge gap, we evaluated the association between concentrations of perflurooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS) and perfluorooctane sulfonic acid (PFOS), and their sum (∑4PFAAs) in DW and serum in Swedish adolescents using weighted least squares regression. We paired serum PFAA concentrations in adolescents (age 10–21 years, n = 790) from the dietary survey Riksmaten Adolescents 2016–17 (RMA) with mean PFAA concentrations in water samples collected in 2018 from waterworks (n = 45) supplying DW to the participant residential and school addresses. The median concentrations of individual PFAAs in DW were < 1 ng/L. Median concentrations of PFNA and PFHxS in serum were < 1 ng/g, while those of PFOA and PFOS were 1–2 ng/g. Significant positive associations between PFAA concentrations in DW and serum were found for all four PFAAs and ∑4PFAAs, with estimated serum/DW concentration ratios ranging from 210 (PFOA) to 670 (PFHxS), taking exposure from sources other than DW (background) into consideration. The mean concentrations of PFHxS and ∑4PFAA in DW that would likely cause substantially elevated serum concentrations above background variation were estimated to 0.9 ng/L and 2.4 ng/L, respectively. The European Food Safety Authority has determined a health concern concentration of 6.9 ng ∑4PFAAs/mL serum. This level was to a large degree exceeded by RMA participants with DW ∑4PFAA concentrations above the maximum limits implemented in Denmark (2 ng ∑4PFAAs/L) and Sweden (4 ng ∑4PFAAs/L) than by RMA participants with DW concentrations below the maximum limits. In conclusion, PFAA exposure from low-level contaminated DW must be considered in risk assessment for adolescents.
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| 36. |
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| 37. |
- Schenk, Linda, 1980-, et al.
(författare)
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A quantitative comparison of the safety margins in the European indicative occupational exposure limits and the derived no-effect levels for workers under REACH
- 2011
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 121:2, s. 408-416
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Tidskriftsartikel (refereegranskat)abstract
- The new European Union (EU) REACH legislation requires Derived No-Effect Levels (DNEL) to be calculated for substances produced in quantities above 10 tonnes/year. Meanwhile, the setting of occupational exposure limits (OEL) continues both at the member state and the EU level. According to REACH, Indicative OEL Values (IOELVs) from the Commission may under some circumstances be used as worker-DNELs. On the other hand, worker-DNELs will be derived for several thousand substances, far more than the roughly 100 substances for which IOELVs have been established. Thus, the procedure to set health-based OELs may become influential on that of DNELs and vice versa. In this study, we compare the safety margins of 88 SCOEL recommendations with those of the corresponding worker-DNELs, derived according to the default approach as described in the REACH guidance document. Overall, the REACH safety margins were approximately six times higher than those derived from the SCOEL documentation but varied widely with REACH/SCOEL safety margin ratios ranging by two orders of magnitude, from 0.3 to 58 (n=88). The discrepancies may create confusion in terms of legal compliance, risk management and risk communication. We also found that the REACH guidance document, although encompassing detailed advice on many issues, including default assessment factors for species and route extrapolation, gives no quantitative guidance on when and how to depart from defaults.
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| 38. |
- Schenk, Linda, et al.
(författare)
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Derived No-effect Levels (DNELs) under the European Chemicals Regulation REACH-An Analysis of Long-term Inhalation Worker-DNELs Presented by Industry
- 2015
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Ingår i: Annals of Occupational Hygiene. - : Oxford University Press (OUP). - 0003-4878 .- 1475-3162. ; 59:4, s. 416-438
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Tidskriftsartikel (refereegranskat)abstract
- The European REACH regulation places responsibility for providing safety information, including derived no-effect levels (DNELs), on chemicals and chemical products on 'industry', i.e. manufacturers and importers. We compared long-term inhalation worker-DNELs (wDNELs) presented by industry with the corresponding Swedish occupational exposure limits (OELs), and for a subset, with wDNELs derived by us. Our wDNELs were derived using toxicological evaluations published by the Swedish Criteria Group and our interpretation of the REACH Guidance. On average, industry's wDNELs were the same as the Swedish OELs (median of wDNEL-OEL ratios: 0.98, n = 235). However, the variation was huge, the extremes being up to 450 times higher, and up to 230 times lower than the corresponding OEL. Nearly one-fifth of the wDNELs were = 2 times higher and one-third = 2 times lower than the OEL. No time trend was seen in the wDNEL/OEL ratios, suggesting that older OELs were not systematically higher than the more recent ones. Industry's wDNELs varied widely and were generally higher (median 4.2 times, up to 435 times higher, down to 13 times lower, n = 23) also compared to our wDNELs. Only five industry wDNELs were equal to or lower than ours. The choices of key studies, dose descriptors, and assessment factors all seemed to contribute to the discrepancies. We conclude that although the REACH guidance is detailed, many choices that will influence the wDNEL lack firm instructions. A major problem is that little advice is given on when and how to depart from default assessment factors.
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| 39. |
- Schenk, Linda, 1980-, et al.
(författare)
-
How consistent are the Derived No-Effect Levels (DNELs) in the European REACH legislation?
- 2013
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Konferensbidrag (refereegranskat)abstract
- The new European REACH regulation places more responsibility than hitherto on manufacturers and importers of chemicals (“industry”) to provide safety information. An important part of the development of a REACH Chemical Safety Report is derivation of Derived No-Effect Levels (DNELs) which represent “the level of exposure above which humans should not be exposed”. In order to study the consistency, we compared DNELs presented by industry at the website of the European Chemicals Agency (ECHA) with those derived by us in our interpretation of the REACH guidance (Chapter R.8: Characterisation of dose [concentration]-response for human health, http://echa.europa.eu/documents/10162/13632/information_requirements_r8_en.pdf). There are various DNELs, e.g. representing short-term, long-term, inhalation and dermal exposure, as well as workers and the whole population. We limited our study to “worker-DNELs long-term” for inhalation route as they resemble occupational exposure limits (OELs). We found 24 substances for which (1) such DNELs were given in the ECHA chemical database (http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances) and (2) a scientific basis for OEL had been published by the Swedish Criteria Group within the last 15 years in the serial Arbete och Hälsa (https://gupea.ub.gu.se/handle/2077/3194?locale=en). The results were startling, as the DNELs given by industry were 2.4 to 1,100 times higher than ours for 23 substances and 260,000 times higher for trimellitic anhydride. Some of the discrepancy is explained by different choice of key studies/points of departure (PODs). However, the choice of assessment factors (AFs) also differed markedly, as industry’s total AFs (calculated implicitly from the POD and the DNEL) were 1-230 times lower than ours. We conclude that although the REACH guidance is relatively detailed, many arbitrary choices remain that will influence the DNEL. A major problem is that little advice is given on when and how to depart from default AFs.
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| 40. |
- Schenk, Linda, 1980-, et al.
(författare)
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Management of bias and conflict of interest among occupational exposure limit expert groups
- 2021
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier BV. - 0273-2300 .- 1096-0295. ; 123
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Tidskriftsartikel (refereegranskat)abstract
- Our aim was to evaluate policies and procedures for management of conflict of interest (CoI) and other sources of bias, implemented in Occupational Exposure Limit (OEL) expert groups. First, we compiled procedural criteria applicable to OEL-setting, based on literature on CoI and systematic reviews. Second, we identified 58 global OEL-sources and sought the underlying expert groups and operating procedures. We identified eleven active groups, of which five have documented CoI policies. In all five, CoI management is based on declarations of interests (DoIs) and removal of experts from decisions in which they have an interest. Notable differences include publication of DoIs (three of five groups), limitation of DoI to current interests (two groups), quantitative limits for financial interests (none specified to ≥€10,000 per interest), control procedures for undisclosed CoI (one group), and procedures in case of discovery of undisclosed CoI (three groups). Methods to evaluate study quality are described by three groups, while reproducible and comprehensive strategies to identify and select data receive less attention. We conclude that procedures to manage CoI and bias are not broadly implemented, or at least not openly and transparently communicated. This lack of visible procedures is remarkable, considering OEL's impact on health and economy.
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| 41. |
- Schenk, Linda, 1980-, et al.
(författare)
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Use of uncertainty factors by the European Commission Scientific Committee on Occupational Exposure Limits : a follow-up
- 2018
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Ingår i: Critical reviews in toxicology. - : TAYLOR & FRANCIS LTD. - 1040-8444 .- 1547-6898. ; 48:7, s. 513-521
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Forskningsöversikt (refereegranskat)abstract
- Decision on the safety margin, for instance by using uncertainty factors (UFs), is a key aspect in setting Occupational Exposure Limits (OELs). We analyzed the UFs in 128 OEL recommendations from the European Commission's Scientific Committee on Occupational Exposure Limits (SCOEL). We investigated factors expected to potentially influence the UFs, as well as a selection of factors that might influence how expert groups perceive quality or reliability of key studies. We extracted UFs explicitly stated in the recommendations (EUFs) and, when EUFs were missing, calculated an implicit safety margin (ISM) by dividing the point of departure (PoD) by the OEL. EUFs and ISMs were lower for recommendations based on human data than those based on animal data. EUFs and ISMs were also lower for No-Observed Adverse Effect Concentrations (NOAECs) than Lowest Observed Adverse Effect Concentrations (LOAECs). We saw no differences based on local vs systemic critical effects. Acute data resulted in lower EUFs and ISMs than subchronic. We saw no influence from status of key study (publication status, performer or funder), but high tonnage substances (1,000,000+ tonnes) have lower EUFs and ISMs than substances currently not registered under REACH. Although SCOEL methodology stated that UF should be documented, only 65 out of 128 OEL recommendations included an EUF. Indeed, the ratio of EUFs to ISMs even decreased from 1991-2003 to 2004-2017. Additionally, EUFs were, on average, 1.8 times higher than ISMs. We conclude that a more articulate framework for using UFs could enhance consistency and transparency of the SCOEL recommendations.
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| 42. |
- Schenk, Linda, et al.
(författare)
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Use of Uncertainty Factors by the SCOEL in their derivation of health-based Occupational Exposure Limits
- 2010
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Ingår i: Critical reviews in toxicology. - : Informa UK Limited. - 1040-8444 .- 1547-6898. ; 40:9, s. 791-798
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Forskningsöversikt (refereegranskat)abstract
- The aim of this study was to investigate how the Scientific Committee on Occupational Exposure Limits (SCOEL) of the European Commission uses uncertainty factors when proposing health-based indicative occupational exposure limit values (IOELVs). In total, 75 IOELVs in 62 summary documents published from 1991 to 2003 were analyzed. For 31 of the IOELVs, no explicit uncertainty factor (EUF) was stated. For these, we calculated an implicit safety margin (ISM) as the ratio between the point of departure (POD, derived from the NOAEL or LOAEL of the critical effect) and the proposed IOELV. We further analysed whether date of recommendation, type of critical effect, nature of POD or amount of available data influenced the magnitude of the EUFs and ISMs. The ISMs varied little (range 1-5), while the EUFs showed more variability (range 1-50). The EUFs remained unaffected over time and the ISMs decreased slightly. Significant differences in the magnitude of the EUFs, but not ISMs, were found between critical effects, however, contrary to expected the average EUFs and ISMs for irritation were similar to those for more severe systemic effects. The nature of the POD affected the ISMs and EUFs only slightly and less than expected. Both EUFs and ISMs showed a weak but significant negative correlation with the amount of available toxicological data, measured as the number of relevant publications in PubMed, whereas SCOEL statements on data sufficiency had no influence. Overall, the most striking difference was that between EUFs and ISMs, the former being on average 2.1 times higher.
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| 43. |
- Schenk, Linda, 1980-, et al.
(författare)
-
Will worker DNELs derived under the European REACH regulation extend the landscape of occupational exposure guidance values?
- 2019
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Ingår i: Archives of Toxicology. - : Springer Berlin/Heidelberg. - 0340-5761 .- 1432-0738. ; 93:5, s. 1187-1200
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Forskningsöversikt (refereegranskat)abstract
- Derived no-effect levels for workers (wDNELs) under the European REACH legislation have many aspects in common with occupational exposure limits (OELs). In an attempt to examine under which circumstances wDNELs might be used as exposure guidance outside their intended application, we compared derivation methods, coverage of substances and numerical values of wDNELs against two regulatory OEL lists (European Commission and Sweden) and three sets of recommendations (European SCOEL, German MAK and US ACGIH). Finally, we looked closer at wDNELs where SCOEL concluded that data were insufficient to derive an OEL. Major differences between wDNELs and OELs include regulatory background, intended use, actors involved, substance selection criteria, transparency and procedure of derivation, and operationalisation in terms of risk management measures. As of summer 2018, approximately five times more substances were covered by wDNELs than by the five sets of OELs examined herein. Meanwhile, many occupationally relevant pollutants were not covered by wDNELs, e.g. one-third of Swedish OELs lack corresponding wDNELs. We also note that wDNELs and OELs for the same substance may vary considerably, up to several orders of magnitude. In conclusion, with extensive substance coverage, wDNELs extend the landscape beyond the OELs. That said, important limitations are (1) that many air pollutants relevant for workers' health are not covered by REACH, and (2) concerns for inconsistencies in the derivation of wDNELs and in their level of protection. In particular, that route-to-route extrapolation is a common practice that may be grossly misleading when the effect of concern is local, e.g. sensitisation.
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| 44. |
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| 45. |
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| 46. |
- Stamyr, Kristin, et al.
(författare)
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Swedish forensic data 1992-2009 suggest hydrogen cyanide as an important cause of death in fire victims
- 2012
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Ingår i: Inhalation Toxicology. - : Informa Healthcare. - 0895-8378 .- 1091-7691. ; 24:3, s. 194-199
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Tidskriftsartikel (refereegranskat)abstract
- Between 60 and 80% of all deaths related to fire are attributed to toxic fumes. Carbon monoxide (CO) is commonly thought to be the major cause. However, hydrogen cyanide (HCN) is also formed. Still, the exact contribution of HCN to fire-related fatalities is unknown. The aim of the study was to investigate the impact of HCN in relation to CO as a cause of death in fire victims. Data on carboxyhemoglobin (COHb) and blood cyanide from deceased fire victims in the period 1992-2009 were collected from two Swedish nationwide forensic databases (ToxBase and RattsBase). The databases contain data on COHb and/or cyanide from 2303 fire victims, whereof 816 on both COHb and cyanide. Nonparametric statistical tests were used. Seventeen percent of the victims had lethal or life-threatening blood cyanide levels (andgt;1 mu g/g) and 32% had lethal COHb levels (andgt;50% COHb). Over 31% had cyanide levels above 0.5 mu g/g, an indication of significant HCN exposure. The percentages may be underestimates, as cyanide is quickly eliminated in blood also after death. Our results support the notion that HCN contributes more to the cause of death among fire victims than previously thought.
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| 47. |
- Wålinder, Robert, et al.
(författare)
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Acute effects of 1-octen-3-ol, a microbial volatile organic compound (MVOC)--an experimental study
- 2008
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Ingår i: Toxicology Letters. - : Elsevier BV. - 0378-4274 .- 1879-3169. ; 181:3, s. 141-7
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Tidskriftsartikel (refereegranskat)abstract
- Acute effects were assessed from exposure to a common volatile compound of microbial origin, the aliphatic alcohol 1-octen 3-ol (octenol). Twenty-nine volunteers performed symptom reports, measurement of blink frequency by electromyography, measurement of the eye break-up time, vital staining of the eye, nasal lavage, acoustic rhinometry, transfer tests and dynamic spirometry. Subjects were during 2h in random order exposed to either 10mg/m(3) of octenol or clean air as control. During octenol exposure subjective ratings of smell and nasal irritation were increased together with higher nasal lavage biomarker levels of eosinophil cationic protein, myeloperoxidase and lysozyme. Also eye irritation and blinking frequency were increased together with throat irritation, mild dyspnoea after 1-h but not after 2-h, and a small decrease in vital capacity. Ratings of headache and nausea were also increased. Atopics did not have more reactions due to exposure, whereas females experienced more smell and mucosal irritation. Thus, there were both subjective and objective signs of mild mucosal irritation of eyes and airways together with symptoms of headache and nausea.
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| 48. |
- Wålinder, Robert, et al.
(författare)
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Acute effects of a fungal volatile compound
- 2005
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 113:12, s. 1775-1778
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: 3-Methylfuran (3-MF) is a common fungal volatile product with active biologic properties, and previous studies have indicated a contribution to airway disease. The aim of the present study was to assess the acute health effects of this compound in humans. DESIGN: Acute effects were assessed via chamber exposure to (1 mg/m3) 3-MF. PARTICIPANTS AND MEASUREMENTS: Twenty-nine volunteers provided symptom reports, ocular electromyograms, measurement of eye tear film break-up time,vital staining of the eye, nasal lavage, acoustic rhinometry, transfer tests, and dynamic spirometry. RESULTS: No subjective ratings were significantly increased during exposure. Blinking frequency and the lavage biomarkers myeloperoxidase and lysozyme were significantly increased, and forced vital capacity was significantly decreased during exposure to 3-MF compared with air control. CONCLUSIONS AND RELEVANCE TO CLINICAL PRACTICE: Acute effects in the eyes, nose, and airways were detected and might be the result of the biologically active properties of 3-MF. Thus, 3-MF may contribute to building-related illness.
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