دورية أكاديمية
Defining embryonic developmental effects of chemical mixtures using the embryonic stem cell test.
| العنوان: | Defining embryonic developmental effects of chemical mixtures using the embryonic stem cell test. |
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| المؤلفون: | van Oostrom CT; Department of Innovative Testing Strategies, Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands., Slob W; Department of Food Safety, Center for Food, Prevention and Care, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands., van der Ven LT; Department of Innovative Testing Strategies, Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. Electronic address: leo.van.der.ven@rivm.nl. |
| المصدر: | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2020 Jun; Vol. 140, pp. 111284. Date of Electronic Publication: 2020 Mar 20. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 8207483 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-6351 (Electronic) Linking ISSN: 02786915 NLM ISO Abbreviation: Food Chem Toxicol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Exeter : Elsevier Science Ltd Original Publication: Oxford ; New York : Pergamon Press, c1982- |
| مواضيع طبية MeSH: | Complex Mixtures/*toxicity , Embryonic Development/*drug effects , Embryonic Stem Cells/*drug effects , Teratogens/*toxicity, Animals ; Dose-Response Relationship, Drug ; Oxidative Stress/drug effects ; Risk Assessment |
| مستخلص: | The embryonic stem cell test (EST) was applied to evaluate dose addition in combined exposures of teratogenic compounds in the EFSA-defined cumulative assessment group "craniofacial malformations", which was one of the selected cases in the EU-H2020 project "EuroMix". Test compounds were selected through reported effects in rodents, and represented a wide variety of chemical families and modes of action (MOA), including triazoles to inhibit CYP26; (synthetic) retinoids, to activate RAR/RXR; valproic acid, to inhibit histone deacetylase; dithiocarbamates, to disrupt extracellular matrix formation; dioxin (-like) compounds, to activate the aryl hydrocarbon receptor; 17alpha-ethynylestradiol, to activate the estrogen receptor; 5-fluorouracil, to disrupt DNA-synthesis; MEHP and PFOS, to activate peroxisome proliferation activated receptors; and methyl mercury, to induce oxidative stress and inhibit protein function. The EST appeared particularly useful to evaluate differentiation-inhibiting effects of compounds targeting early processes in craniofacial development, possibly related to the early fate of neural crest cells. Mixtures, designed as equipotent concentrations of two compounds with similar or dissimilar MOA, and single compounds showed overlapping dose-responses. This observation is consistent with dose addition in the EST in all studied binary mixtures, irrespective of MOA, and thereby supports the application of dose-addition as a default in cumulative risk assessment. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2020 Elsevier Ltd. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Craniofacial malformations; Dose-addition; Embryonic stem cell test; EuroMix; Mixture toxicology |
| المشرفين على المادة: | 0 (Complex Mixtures) 0 (Teratogens) |
| تواريخ الأحداث: | Date Created: 20200325 Date Completed: 20210219 Latest Revision: 20210219 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.fct.2020.111284 |
| PMID: | 32205227 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-6351 |
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| DOI: | 10.1016/j.fct.2020.111284 |