1 Ocak 2021 Dergi makalesi Açık Erişim

Hogberg, Helena T.; da Silveira E Sa, Rita de Cassia; Kleensang, Andre; Bouhifd, Mounir; Cemiloglu Ulker, Ozge; Smirnova, Lena; Behl, Mamta; Maertens, Alexandra; Zhao, Liang; Hartung, Thomas

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    "creators": [
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        "affiliation": "Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing CAAT, Baltimore, MD 21205 USA", 
        "name": "Hogberg, Helena T."
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      {
        "name": "da Silveira E Sa, Rita de Cassia"
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      {
        "affiliation": "Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing CAAT, Baltimore, MD 21205 USA", 
        "name": "Kleensang, Andre"
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      {
        "affiliation": "Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing CAAT, Baltimore, MD 21205 USA", 
        "name": "Bouhifd, Mounir"
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      {
        "name": "Cemiloglu Ulker, Ozge"
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      {
        "affiliation": "Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing CAAT, Baltimore, MD 21205 USA", 
        "name": "Smirnova, Lena"
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      {
        "affiliation": "NIEHS, Natl Toxicol Program, Durham, NC USA", 
        "name": "Behl, Mamta"
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      {
        "affiliation": "Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing CAAT, Baltimore, MD 21205 USA", 
        "name": "Maertens, Alexandra"
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      {
        "name": "Zhao, Liang"
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      {
        "name": "Hartung, Thomas"
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    ], 
    "description": "Due to regulatory bans and voluntary substitutions, halogenated polybrominated diphenyl ether (PBDE) flame retardants (FR) are increasingly substituted by mainly organophosphorus FR (OPFR). Leveraging a 3D rat primary neural organotypic in vitro model (rat brainsphere), we compare developmental neurotoxic effects of BDE-47-the most abundant PBDE congener-with four OPFR (isopropylated phenyl phosphate-IPP, triphenyl phosphate-TPHP, isodecyl diphenyl phosphate-IDDP, and tricresyl phosphate (also known as trimethyl phenyl phosphate)-TMPP). Employing mass spectroscopy-based metabolomics and transcriptomics, we observe at similar human-relevant non-cytotoxic concentrations (0.1-5 mu M) stronger developmental neurotoxic effects by OPFR. This includes toxicity to neurons in the low mu M range; all FR decrease the neurotransmitters glutamate and GABA (except BDE-47 and TPHP). Furthermore,n-acetyl aspartate (NAA), considered a neurologic diagnostic molecule, was decreased by all OPFR. At similar concentrations, the FR currently in use decreased plasma membrane dopamine active transporter expression, while BDE-47 did not. Several findings suggest astrogliosis induced by the OPFR, but not BDE-47. At the 5 mu M concentrations, the OPFR more than BDE-47 interfered with myelination. An increase of cytokine gene and receptor expressions suggests that exposure to OPFR may induce an inflammatory response. Pathway/category overrepresentation shows disruption in 1) transmission of action potentials, cell-cell signaling, synaptic transmission, receptor signaling, (2) immune response, inflammation, defense response, (3) cell cycle and (4) lipids metabolism and transportation. Taken together, this appears to be a case of regretful substitution with substances not less developmentally neurotoxic in a primary rat 3D model.", 
    "doi": "10.1007/s00204-020-02903-2", 
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      "issue": "1", 
      "pages": "207-228", 
      "title": "ARCHIVES OF TOXICOLOGY", 
      "volume": "95"
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    "license": {
      "id": "cc-by"
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    "publication_date": "2021-01-01", 
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      "title": "Dergi makalesi", 
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    "title": "Organophosphorus flame retardants are developmental neurotoxicants in a rat primary brainsphere in vitro model"
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