| 1. |
- Gupta, G, et al.
(författare)
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ToxPoint: Copper Is the New Showstopper
- 2022
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Ingår i: Toxicological sciences : an official journal of the Society of Toxicology. - : Oxford University Press (OUP). - 1096-0929. ; 189:1, s. 3-4
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Lomphithak, T, et al.
(författare)
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Die hard: cell death mechanisms and their implications in nanotoxicology
- 2023
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Ingår i: Toxicological sciences : an official journal of the Society of Toxicology. - : Oxford University Press (OUP). - 1096-0929.
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Tidskriftsartikel (refereegranskat)abstract
- Cell death is a fundamental biological process, and its fine-tuned regulation is required for life. However, the complexity of regulated cell death is often reduced to a matter of live-dead discrimination. Here, we provide a perspective on programmed or regulated cell death, focusing on apoptosis, pyroptosis, necroptosis, and ferroptosis (the latter three cell death modalities are examples of regulated necrosis). We also touch on other, recently described manifestations of (pathological) cell death including cuproptosis. Furthermore, we address how engineered nanomaterials impact on regulated cell death. We posit that an improved understanding of nanomaterial-induced perturbations of cell death may allow for a better prediction of the consequences of human exposure to these materials and could also yield novel approaches by which to mitigate their effects. Finally, we provide examples of the harnessing of nanomaterials to achieve cancer cell killing through the induction of regulated cell death.
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| 3. |
- Manz, Katherine E., et al.
(författare)
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Targeted and Nontargeted Detection and Characterisation of Trace Organic Chemicals in Human Serum and Plasma Using QuEChERS Extraction
- 2022
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 185:1, s. 77-88
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Tidskriftsartikel (refereegranskat)abstract
- Humans are exposed to a broad range of organic chemicals. Although targeted gas chromatography mass spectrometry techniques are used to quantify a limited number of persistent organic pollutants and trace organic contaminants in biological samples, nontargeted, high-resolution mass spectrometry (HRMS) methods assess the human exposome more extensively. We present a QuEChERS extraction for targeted and nontargeted analysis of trace organic contaminants using HRMS and compare this method to a traditional, cartridge-based solid-phase extraction (SPE). Following validation using reference and spiked serum samples, the method was applied to plasma samples (n = 75) from the Prospective investigation of Obesity, Energy, and Metabolism (POEM) study. We quantified 44 analytes using targeted analysis and 6247 peaks were detected using the nontargeted approach. Over 90% of targeted analytes were at least 90% recovered using the QuEChERS method in spiked serum samples. In nontargeted analysis, 84% of the peaks were above the method detection limit with area counts up to 3.0 x 10(5) times greater using the QuEChERS method. Of the targeted compounds, 88% were also identified in the nontargeted analysis. We categorized the 4212 chemicals assigned an identity in using EPA's CompTox Dashboard and 1076 chemicals were found in at least one list. The category with the highest number of chemicals was "androgen or estrogen receptor activity." The findings demonstrate that a QuEChERS technique is suitable for both targeted and nontargeted analysis of trace organic contaminants in biological samples.
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| 4. |
- Mentor, Anna, 1989-, et al.
(författare)
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Bisphenol AF and Bisphenol F Induce Similar Feminizing Effects in Chicken Embryo Testis as Bisphenol A
- 2020
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Ingår i: Toxicological Sciences. - OXFORD ENGLAND : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 178:2, s. 239-250
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Tidskriftsartikel (refereegranskat)abstract
- The plastic component bisphenol A (BPA) impairs reproductive organ development in various experimental animal species. In birds, effects are similar to those caused by other xenoestrogens. Because of its endocrine disrupting activity, BPA is being substituted with other bisphenols in many applications. Using the chicken embryo model, we explored whether the BPA alternatives bisphenol AF (BPAF), bisphenol F (BPF), and bisphenol S (BPS) can induce effects on reproductive organ development similar to those induced by BPA. Embryos were exposed in ovo from embryonic day 4 (E4) to vehicle, BPAF at 2.1, 21, 210, and 520 nmol/g egg, or to BPA, BPF, or BPS at 210 nmol/g egg and were dissected on embryonic day 19. Similar to BPA, BPAF and BPF induced testis feminization, manifested as eg testis-size asymmetry and ovarian-like cortex in the left testis. In the BPS-group, too few males were alive on day 19 to evaluate any effects on testis development. We found no effects by any treatment on ovaries or Mullerian ducts. BPAF and BPS increased the gallbladder-somatic index and BPAF, BPF and BPS caused increased embryo mortality. The overall lowest-observed-adverse-effect level for BPAF was 210 nmol/g egg based on increased mortality, increased gallbladder-somatic index, and various signs of testis feminization. This study demonstrates that the BPA replacements BPAF, BPF, and BPS are embryotoxic and suggests that BPAF is at least as potent as BPA in inducing estrogen-like effects in chicken embryos. Our results support the notion that these bisphenols are not safe alternatives to BPA.
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| 5. |
- Svingen, T, et al.
(författare)
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A Pragmatic Approach to Adverse Outcome Pathway Development and Evaluation
- 2021
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Ingår i: Toxicological sciences : an official journal of the Society of Toxicology. - : Oxford University Press (OUP). - 1096-0929. ; 184:2, s. 183-190
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Tidskriftsartikel (refereegranskat)abstract
- The adverse outcome pathway (AOP) framework provides a practical means for organizing scientific knowledge that can be used to infer cause-effect relationships between stressor events and toxicity outcomes in intact organisms. It has reached wide acceptance as a tool to aid chemical safety assessment and regulatory toxicology by supporting a systematic way of predicting adverse health outcomes based on accumulated mechanistic knowledge. A major challenge for broader application of the AOP concept in regulatory toxicology, however, has been developing robust AOPs to a level where they are peer reviewed and accepted. This is because the amount of work required to substantiate the modular units of a complete AOP is considerable, to the point where it can take years from start to finish. To help alleviate this bottleneck, we propose a more pragmatic approach to AOP development whereby the focus becomes on smaller blocks. First, we argue that the key event relationship (KER) should be formally recognized as the core building block of knowledge assembly within the AOP knowledge base (AOP-KB), albeit framing them within full AOPs to ensure regulatory utility. Second, we argue that KERs should be developed using systematic review approaches, but only in cases where the underlying concept does not build on what is considered canonical knowledge. In cases where knowledge is considered canonical, rigorous systematic review approaches should not be required. It is our hope that these approaches will contribute to increasing the pace at which the AOP-KB is populated with AOPs with utility for chemical safety assessors and regulators.
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| 6. |
- Thrikawala, Savini, et al.
(författare)
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Triazole fungicides induce adipogenesis and repress osteoblastogenesis in zebrafish
- 2023
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 193:2, s. 119-130
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Tidskriftsartikel (refereegranskat)abstract
- Triazoles are a major group of azole fungicides commonly used in agriculture, and veterinary and human medicine. Maternal exposure to certain triazole antifungal medication causes congenital malformations, including skeletal malformations. We hypothesized that triazoles used as pesticides in agriculture also pose a risk of causing skeletal malformations in developing embryos. In this study, teratogenic effects of three commonly used triazoles, cyproconazole, paclobutrazol, and triadimenol, were investigated in zebrafish, Danio rerio. Exposure to the triazole fungicides caused bone and cartilage malformations in developing zebrafish larvae. Data from whole-embryo transcriptomics with cyproconazole suggested that exposure to this compound induces adipogenesis while repressing skeletal development. Confirming this finding, the expression of selected bone and cartilage marker genes were significantly downregulated with triazoles exposure as determined by quantitative PCR. The expression of selected adipogenic genes was upregulated by the triazoles. Furthermore, exposure to each of the three triazoles induced adipogenesis and lipid droplet formation in vitro in 3T3-L1 pre-adipocyte cells. In vivo in zebrafish larvae, cyproconazole exposure caused lipid accumulation. These results suggest that exposure to triazoles promotes adipogenesis at the expense of skeletal development, and thus they expand the chemical group of bona fide bone to fat switchers.
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