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  • 1
    In: Environmental Toxicology and Chemistry, Wiley, Vol. 34, No. 12 ( 2015-12), p. 2864-2869
    Abstract: The threshold of toxicological concern (TTC) concept is well established for assessing human safety of food‐contact substances and has been reapplied for a variety of endpoints, including carcinogenicity, teratogenicity, and reproductive toxicity. The TTC establishes an exposure level for chemicals below which no appreciable risk to human health or the environment is expected, based on a de minimis value for toxicity identified for many chemicals. Threshold of toxicological concern approaches have benefits for screening‐level risk assessments, including the potential for rapid decision‐making, fully utilizing existing knowledge, reasonable conservativeness for chemicals used in lower volumes (low production volume chemicals (e.g., 〈 1 t/yr), and reduction or elimination of unnecessary animal tests. Higher production volume chemicals ( 〉 1 t/yr) would in principle always require specific information because of the presumed higher exposure potential. The TTC approach has found particular favor in the assessment of chemicals used in cosmetics and personal care products, as well as other chemicals traditionally used in low volumes. Use of the TTC in environmental safety is just beginning, and initial attempts are being published. Key questions focus on hazard extrapolation of diverse taxa across trophic levels, importance of mode of action, and whether safe concentrations for ecosystems estimated from acute or chronic toxicity data are equally useful and in what contexts. The present study provides an overview of the theoretical basis for developing an ecological (eco)‐TTC, with an initial exploration of chemical assessment and boundary conditions for use. An international collaboration under the International Life Sciences Institute Health and Environmental Sciences Institute has been established to address challenges related to developing and applying useful eco‐TTC concepts. Environ Toxicol Chem 2015;34:2864–2869. © 2015 SETAC
    Type of Medium: Online Resource
    ISSN: 0730-7268 , 1552-8618
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2027441-5
    SSG: 12
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  • 2
    In: Stem Cell Research & Therapy, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2016-12)
    Abstract: Human mesenchymal stromal cells (MSCs) can be isolated from different sources including bone marrow and term placenta. These two populations display distinct patterns of proliferation and differentiation in vitro. Since proliferation and differentiation of cells are modulated by cell–matrix interactions, we investigated the attachment of MSCs to a set of peptide-coated surfaces and explored their interactions with peptides in suspension. Methods Human MSCs were isolated from bone marrow and term placenta and expanded. Binding of MSCs to peptides was investigated by a cell-attachment spot assay, by blocking experiments and flow cytometry. The integrin expression pattern was explored by a transcript array and corroborated by quantitative reverse transcription polymerase chain reaction and flow cytometry. Results Expanded placenta-derived MSCs (pMSCs) attached well to surfaces coated with fibronectin-derived peptides P7, P15, and P17, whereas bone marrow-derived MSCs (bmMSCs) attached to P7, but barely to P15 and P17. The binding of bmMSCs and pMSCs to the peptides was mediated by β1 integrins. In suspension, expanded bmMSCs barely bind to P7, P13, P15, and less to P14 and P17. Ex vivo, bmMSCs failed to bind P7, but displayed a weak interaction with P13, P14, and P15. In suspension, expanded pMSCs displayed binding to many peptides, including P4, P7, P13, P14, P15, and P17. The differences observed in binding of bmMSCs and pMSCs to the peptides were associated with significant differences in expression of integrin α2-, α4-, and α6-chains. Conclusions Human bmMSCs and pMSCs show distinct patterns of attachment to defined peptides and maintain differences in expression of integrins in vitro. Interactions of ex vivo bmMSCs with a given peptide yield different staining patterns compared to expanded bmMSCs in suspension. Attachment of expanded MSCs to peptides on surfaces is different from interactions of expanded MSCs with peptides in suspension. Studies designed to investigate the interactions of human MSCs with peptide-augmented scaffolds or peptides in suspension must therefore regard these differences in cell–peptide interactions.
    Type of Medium: Online Resource
    ISSN: 1757-6512
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2548671-8
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