ArticleArchives of toxicology2021
Organophosphorus flame retardants are developmental neurotoxicants in a rat primary brainsphere in vitro model.
Article in Archives of toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 72 citations in OpenAlex.
- Biodegradation of Triphenyl Phosphate byToxics · 2026Article
- Epigenome-wide association analysis of prenatal organophosphate ester flame retardant exposure in maternal blood implicates maternal immune and neuronal epigenetic alterations.Environment international · 2026Article
- The application progress of organoid technology in the toxicity assessment of environmental pollutants.Cell biology and toxicology · 2026Review
- Article
- Associations between brominated and organophosphate flame retardant levels and inflammatory biomarkers in maternal blood, cord blood, and placental tissue at mid-gestation.The Science of the total environment · 2025Article
- Organophosphate Flame Retardants, Obesity, and Depressive Symptoms among 1019 Young Healthy Men.Environment & health (Washington, D.C.) · 2025Article
- Developmental immunotoxicity study of tris(chloropropyl) phosphate in Hsd:Sprague Dawley SD rats exposed through dosed feed.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Toxicity Assessment of Organophosphate Flame Retardants Using New Approach Methodologies.Toxics · 2025Review
- Elucidating the mechanism of triphenyl phosphate interference in bone metabolism via network toxicology and molecular docking methodologies.Frontiers in endocrinology · 2025Article
- Gestational organophosphate esters (OPEs) and executive function in adolescence: The HOME Study.Environmental research · 2024Article
- Article
- Pervasive environmental chemicals impair oligodendrocyte development.Nature neuroscience · 2024Article
- Exposure to OPFRs Is Associated with Obesity and Dysregulated Serum Lipid Profiles: Data from 2017-2018 NHANES.Metabolites · 2024Article
- Prenatal exposures to organophosphate ester metabolites and early motor development in the MADRES cohort.Environmental pollution (Barking, Essex : 1987) · 2024Article
- Elucidating the toxicity mechanisms of organophosphate esters by adverse outcome pathway network.Archives of toxicology · 2024Article
- Article
- 3D human stem-cell-derived neuronal spheroids forCurrent research in toxicology · 2024Article
- Developmental organophosphate flame retardant exposure disrupts adult hippocampal neurogenesis in Wistar rats.Neurotoxicology · 2023Article
- Gestational exposure to FireMaster® 550 (FM 550) disrupts the placenta-brain axis in a socially monogamous rodent species, the prairie vole (Microtus ochrogaster).Molecular and cellular endocrinology · 2023Article
- Prenatal exposures to organophosphate ester metabolite mixtures and children's neurobehavioral outcomes in the MADRES pregnancy cohort.Environmental health : a global access science source · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 4 countries.
Funding
Abstract
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 µM) stronger developmental neurotoxic effects by OPFR. This includes toxicity to neurons in the low µM 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 µM 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.