The use of human induced pluripotent stem cells to screen for developmental toxicity potential indicates reduced potential for non-combusted products, when compared to cigarettes
| Autor: | Fan Yu, Roman Wieczorek, Edgar Trelles Sticken, Matthew Stevenson, Kathryn Rudd, Lukasz Czekala, Fiona Chapman, Lisa Maria Bode, Liam Simms, Tanvir Walele, Jessica Palmer |
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| Rok vydání: | 2020 |
| Předmět: |
Health
Toxicology and Mutagenesis OECD Organisation for Economic Co-operation and Development Developmental toxicity HTP heated tobacco product Pharmacology Toxicology Applied Microbiology and Biotechnology Nicotine EVP electronic vapour product chemistry.chemical_compound HPLC-DAD high-performance liquid chromatography with a diode-array detector Induced pluripotent stem cell Cytotoxicity CDC Centers for Disease Control and Prevention ISO International Organization for Standardisation Human induced pluripotent stem cells Q-TOF Quadrupole Time-of-Flight EPA United States Environmental Protection Agency bPBS bubbled phosphate buffered saline E-cigarettes TT21C toxicity testing in the 21st century iPS cells induced pluripotent stem cells COT United Kingdom Committee on Toxicity of Chemicals in Food Consumer Products and the Environment medicine.drug DART developmental and reproductive toxicity NICE National Institute for Health and Care Excellence NHS United Kingdom National Health Service FDR false discovery rate ECVAM European Center for the Validation of Alternative Methods nAChRs nicotinic acetylcholine receptors Article ROS reactive oxygen species PBS phosphate buffered saline lcsh:RA1190-1270 medicine devTOXqP devTOX quickPredict Viability assay HYB hybrid product o/c ornithine/cystine ratio e-cigarettes electronic cigarettes lcsh:Toxicology. Poisons ComputingMethodologies_COMPUTERGRAPHICS Smoke LOQ limit of quantification PG/VG propylene glycol/vegetable glycerine Cigarettes TP cell viability toxicity potential concentration CV coefficient of variation UPLC-HRMS ultra-high performance liquid chromatography coupled high resolution mass spectrometry DNPH 2 4-dinitrophenylhydrazine Embryonic stem cell In vitro reproduction assay POD point of difference chemistry HPHCs Harmful and Potentially Harmful Constituents ISTD internal standard dTP developmental toxicity potential concentration ODC ornithine decarboxylase ND No effect was detected within the exposure range tested ATRA All-trans-retinoic acid dTT developmental toxicity threshold LC-MS/MS liquid chromatography with tandem mass spectrometry Toxicant |
| Zdroj: | Current Research in Toxicology Current Research in Toxicology, Vol 1, Iss, Pp 161-173 (2020) |
| ISSN: | 2666-027X |
| Popis: | Graphical abstract Highlights • Effective in vitro strategies are required to predict early developmental toxicity. • devTOXqP is a metabolomics biomarker assay using iPSCs. • Sample smoke/aerosol captured in bPBS, was tested up to 10% concentration. • Cigarettes & HTP bPBS extracts were predicted as potentially developmentally toxic. • HYB & EVP aerosols were not predicted as having developmentally toxic potential in devTOXqP. devTOX quickPredict (devTOXqP) is a metabolomics biomarker-based assay that utilises human induced pluripotent stem (iPS) cells to screen for potential early stage embryonic developmental toxicity in vitro. Developmental toxicity potential is assessed based on the assay endpoint of the alteration in the ratio of key unrelated biomarkers, ornithine and cystine (o/c). This work aimed to compare the developmental toxicity potential of tobacco-containing and tobacco-free non-combustible nicotine products to cigarette smoke. Smoke and aerosol from test articles were produced using a Vitrocell VC10 smoke/aerosol exposure system and bubbled into phosphate buffered saline (bPBS). iPS cells were exposed to concentrations of up to 10% bPBS. Assay sensitivity was assessed through a spiking study with a known developmental toxicant, all-trans-retinoic acid (ATRA), in combination with cigarette smoke extract. The bPBS extracts of reference cigarettes (1R6F and 3R4F) and a heated tobacco product (HTP) were predicted to have the potential to induce developmental toxicity, in this screening assay. The bPBS concentration at which these extracts exceeded the developmental toxicity threshold was 0.6% (1R6F), 1.3% (3R4F), and 4.3% (HTP) added to the cell media. Effects from cigarette smoke and HTP aerosol were driven largely by cytotoxicity, with the cell viability and o/c ratio dose–response curves crossing the developmental toxicity thresholds at very similar concentrations of added bPBS. The hybrid product and all the electronic cigarette (e-cigarette) aerosols were not predicted to be potential early developmental toxicants, under the conditions of this screening assay. |
| Databáze: | OpenAIRE |
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