1.
Selin, Erica, et al.
(författare)
Food contact materials: an effect-based evaluation of the presence of hazardous chemicals in paper and cardboard packaging
2021
Ingår i: Food Additives & Contaminants. - : Informa UK Limited. - 1944-0049 .- 1944-0057. ; 38:9, s. 1594-1607
Tidskriftsartikel (refereegranskat) abstract
Food contact materials (FCMs) can contain hazardous chemicals that may have the potential to migrate into food and pose a health hazard for humans.Previous studies have mainly focused on plastic materials, while data on packaging materials made from paper and cardboard are limited.We used a panel of cell-based bioassays to investigate the presence and impact of bioactive chemicals on human relevant endpoints like oxidative stress, genotoxicity, inflammation, xenobiotic metabolism and endocrine system effects in extracts made from paper and cardboard.In total, 23 methanol extracts of commonly used paper and cardboard available on the Swedish market were extracted as a whole product using methanol to retrieve polar substances, and tested at concentrations 0.3–10 mg/mL and 0.2–6 mg/mL. At the highest concentration bioactivities were observed in a high proportion of the samples: oxidative stress (52%), genotoxicity (100%), xenobiotic metabolism (74%), antiandrogenic- (52%) and antioestrogenic receptor (39%).Packages of potential concern included cake/pastry boxes/mats, boxes for infant formula/skimmed milk, pizza boxes, pizza slice trays and bag of cookies.It should be noted that the extraction for packages like cake/pastry boxes can be considered exaggerated, as the exposure usually is shorter. It can be hypothesised that the observed responses may be explained by inks, coatings, contaminants and/or naturally occurring compounds within the material.To summarise, an effect-based approach enables hazard identification of chemicals within FCMs, which is a valuable tool for ensuring safe use of FCMs.
2.
Oskarsson, Agneta, et al.
(författare)
Antiandrogenic activity and bioavailability of magnolol analogs – A potential for prostate cancer therapeutics
2023
Ingår i: Phytomedicine Plus. - 2667-0313. ; 3
Tidskriftsartikel (refereegranskat) abstract
Background: Prostate cancer is the second most common form of cancer in men worldwide and there is a great need for novel treatment strategies, especially for castrate-resistant prostate cancers where the proliferation of the cancer cells is stimulated by androgens produced in the adrenal cortex and the cancer cells. Purpose: In this study, we have investigated the antiandrogenic properties of magnolol and ten synthetic analogs in vitro. Study design and methods: The compounds were evaluated for cytotoxicity, antiandrogenic receptor activity, binding to the androgen receptor, effects on the production of Prostate-specific antigen (PSA), and potential to pass over a tight layer of Caco-2 cells mimicking gastrointestinal absorption. Results: We found that almost all investigated compounds were antiandrogenic in an androgen receptor reporter gene assay, with IC50 values ranging from 7 to 86 µM. Magnolol itself had the highest antiandrogenic potency. Five of the compounds were then evaluated for their binding to the androgen receptor and three of these compounds were found to bind to the receptor. These five compounds were also evaluated for their effect on the PSA production and four were found to decrease PSA production at non-cytotoxic concentrations. The antiandrogenic activity after passage through a layer of Caco-2 cells, mimicking gastrointestinal absorption, was also evaluated for three of the compounds. All three compounds were found to have the capacity to be transported from the apical to the basolateral side of the Caco-2 cell layer and exert antiandrogenic effects after the transport. Conclusion: In conclusion, this study shows that magnolol and analogs have antiandrogenic effects in vitro and that selected analogs can pass over a tight layer of Caco-2 cells, indicating a potential for good bioavailability after oral administration. These magnolol analogs thereby constitute an interesting group of compounds worthy of further evaluation as potential anti-prostate cancer therapeutics.
3.
Lungu-Mitea, Sebastian, et al.
(författare)
Modeling Bioavailable Concentrations in Zebrafish Cell Lines and Embryos Increases the Correlation of Toxicity Potencies across Test Systems
2021
Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 55:1, s. 447-457
Tidskriftsartikel (refereegranskat) abstract
Linking cellular toxicity to low-tier animal toxicity and beyond is crucial within the adverse outcome pathway concept and the 3R framework. This study aimed to determine and compare the bioavailable effect concentrations in zebrafish cell lines and embryos. Acute, short-term toxicity (48 h) of eight veterinary pharmaceuticals was measured in two zebrafish cell lines (hepatocytes, fibroblasts) and zebrafish embryos. Seven endpoints of cytotoxicity were recorded. The fish embryo acute toxicity test was modified by adding sublethal endpoints. Chemical distribution modeling (mass balance) was applied to compute the bioavailable compound concentrations in cells (C-free) and embryos (C-int;aq) based on nominal effect concentrations (C-nom). Effect concentration ratios were calculated (cell effects/embryo effects). A low correlation was observed between cytotoxicity and embryo toxicity when nominal concentrations were used. Modeled bioavailable effect concentrations strongly increased correlations and placed regression lines close to the line of unity and axis origin. Cytotoxicity endpoints showed differences in sensitivity and predictability. The hepatocyte cell line depicted closer proximity to the embryo data. Conclusively, the high positive correlation between the cell- and embryo-based test systems emphasizes the appropriate modulation of toxicity when linked to bioavailable concentrations. Furthermore, it highlights the potential of fish cell lines to be utilized in integrated testing strategies.
4.
Selin, Erica, et al.
(författare)
Hazardous chemicals in non‑polar extracts from paper and cardboard food packaging: an effect‑based evaluation
2022
Ingår i: Environmental Sciences Europe. - Stockholm : IVL Svenska Miljöinstitutet AB. - 2190-4707 .- 2190-4715. ; 34:1
Tidskriftsartikel (refereegranskat) abstract
Background: Food contact articles are used in our everyday life and information regarding the potential health hazards of migrating chemicals for humans is scarce. In this study, an effect-based evaluation of non-polar extracts of food contact articles made of paper and board was conducted with a panel of eight bioassay endpoints. These, health-relevant endpoints, included oxidative stress, inflammation, genotoxicity, xenobiotic metabolism and hormone receptor effects.Results: In total, 62 food contact articles were pooled into 19 groups, in which articles intended to be used for similar types of food item(s) were pooled, and extracted with acetone:n-hexane (1:4). These were then tested in the effectbased bioassays. Bioactivities were detected for multiple materials in six out of eight assays, the two assays showing no effects were NFκB and androgen receptor agonistic response. In essence, the detection rates of the tested non-polar extracts were 72% for antagonistic effects on the estrogen receptor, 72% for antagonistic effects on the androgen receptor, 47% for oxidative stress, 28% for agonistic effects on the estrogen receptor and 33% for genotoxicity. The bioequivalent concentrations ranges in extracts of 10 mg food contact article/mL cell culture media were: for oxidative stress from 2.45 to 5.64 μM tBHQ equivalents, estrogen receptor agonistic activity from 1.66 to 6.33 ρM estradiol equivalents, estrogen receptor antagonistic activity from 1.21 × 10–3 to 4.20 × 10–3 μM raloxifene equivalents and androgen antagonistic activity 0.08–0.46 μM hydroxyflutamide equivalents.The extracts that were bioactive in multiple assays were: baking moulds, boxes for popcorn, infant formula/skimmed milk, porridge/flour mixes, pizza, fries’ and hamburgers as well as packages for frozen food.Conclusion: Non-polar extracts of food contact articles contain compounds that can activate molecular initiating events in toxicity pathways of high relevance to human health. These events included endocrine-disruptive activities, oxidative stress and genotoxicity. Effect-based methods proved to be a valuable tool for evaluating food package articles, as they can detect potentially hazardous effects of both known and unknown chemicals as well as potentialcocktail effects.
5.
Oskarsson, Agneta
(författare)
Molybdenum
2022
Ingår i: Handbook on the Toxicology of Metals : Volume II: Specific Metals. - 9780128229460 ; 2, s. 601-614
Bokkapitel (refereegranskat) abstract
Molybdenum is an essential element, required as a component of enzymes involved in, that is, the catabolism of sulfur amino acids and nucleotides. Dietary recommendations have been established and human intake is usually within the range of the recommendations. Soluble molybdenum compounds are readily absorbed when ingested, and data supporting absorption after inhalation have also been presented in experimental animals and occupationally exposed humans. The highest molybdenum concentrations are found in the kidneys and liver. Excretion, primarily through the urine, is rapid. The biological half-life in blood ranges from a few hours to a few days.The metabolism of molybdenum is affected by copper and sulfur intake. In livestock, chronic molybdenum poisoning (known as teart disease) is caused by feed high in molybdenum and low in copper. Symptoms include anemia, gastrointestinal disturbances, bone disorders, and growth retardation.In laboratory animals, excessive molybdenum may give rise to morphological and functional changes in the kidneys. Reproductive toxicity of molybdenum has been reported, but not reproduced in more recent OECD guideline studies. Molybdenum trioxide was carcinogenic to animals (mice and rats) in long-term GLP studies. Lung fibrosis was observed at high doses.Increased blood uric acid values and gout-like symptoms have been reported among exposed workers, as well as among the general population living in an area with a high-molybdenum and low-copper content in the soil and vegetables. Epidemiological studies indicate an accelerated decline in glomerular filtration rate, also impaired semen quality and an increased risk for stroke have been reported but remain to be confirmed.Molybdenum toxicity and essentiality have been reviewed, that is, by Novotny (2011), World Health Organization (WHO, 2011), Mendel and Kruse (2012), EFSA (2013), IARC (2019), and ATSDR (2020).
6.
Rosenmai, Anna, et al.
(författare)
The toxicity of the methylimidazolium ionic liquids, with a focus on M8OI and hepatic effects
2020
Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 136
Tidskriftsartikel (refereegranskat) abstract
Ionic liquids are a diverse range of charged chemicals with low volatility and often liquids at ambient temperatures. This characteristic has in part lead to them being considered environmentally-friendly replacements for existing volatile solvents. However, methylimidazolium ionic liquids are slow to break down in the environment and a recent study at Newcastle detected 1 octyl 3 methylimidazolium (M8OI) - an 8 carbon variant methylimidazolium ionic liquid - in soils in close proximity to a landfill site. The current M8OI toxicity database in cultured mammalian cells, in experimental animal studies and in model indicators of environmental impact are reviewed. Selected analytical data from the Newcastle study suggest the soils in close proximity to the landfill site, an urban soil lacking overt contamination, had variable levels of M8OI. The potential for M8OI - or a structurally related ionic liquid - to trigger primary biliary cholangitis (PBC), an autoimmune liver disease thought to be triggered by an unknown agent(s) in the environment, is reviewed.
