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@article{1548905, author = {Bajard ép.Esner, Lola Murielle and Melymuk, Lisa Emily and Bláha, Luděk}, article_location = {HEIDELBERG, GERMANY}, article_number = {February}, doi = {http://dx.doi.org/10.1186/s12302-019-0195-z}, keywords = {Flame retardants; ToxCast; AOP; Prioritization; Hazard; Mechanisms of toxicity}, language = {eng}, issn = {2190-4715}, journal = {Environmental Sciences Europe}, title = {Prioritization of hazards of novel flame retardants using the mechanistic toxicology information from ToxCast and Adverse Outcome Pathways}, url = {https://enveurope.springeropen.com/articles/10.1186/s12302-019-0195-z}, volume = {31}, year = {2019} }
TY - JOUR ID - 1548905 AU - Bajard ép.Esner, Lola Murielle - Melymuk, Lisa Emily - Bláha, Luděk PY - 2019 TI - Prioritization of hazards of novel flame retardants using the mechanistic toxicology information from ToxCast and Adverse Outcome Pathways JF - Environmental Sciences Europe VL - 31 IS - February SP - 1-19 EP - 1-19 PB - Springer-Verlag, GmbH, Environmental Sciences Europe SN - 21904715 KW - Flame retardants KW - ToxCast KW - AOP KW - Prioritization KW - Hazard KW - Mechanisms of toxicity UR - https://enveurope.springeropen.com/articles/10.1186/s12302-019-0195-z L2 - https://enveurope.springeropen.com/articles/10.1186/s12302-019-0195-z N2 - BackgroundFlame retardants (FRs) are used in most consumer products and textiles to comply with current flammability standards. After the restriction of polybrominated diphenyl ethers, a large number of chemically diverse replacement FRs are increasingly used, but the risk they represent is not yet properly evaluated and their toxicity pathways are still poorly understood.ApproachWe collected in vivo toxicological information on 62 (including 52 non-regulated) FRs and established five prioritization categories (Cat I to V) based on data availability and toxicological concern. We then considered available in vitro toxicological data from ToxCast, as a complement to in vivo information. By combining these information sources, we then explored relevant toxicity mechanisms for nine selected FRs (Cat I) using the AOP (Adverse Outcome Pathway) framework.ResultsFor 20 FRs (Cat V), toxicological data on mammals were absent. Data available were scarce for another 22 FRs, of which 14 FRs (Cat II) may be of toxicological concern. We found substantial information for only ten replacement FRs, of which nine (Cat I) present some toxicological concern: tris-2-chloroethyl phosphate (TCEP), tris(1,3-dichloropropyl)phosphate (TDCIPP), triphenyl phosphate (TPhP), tricresyl phosphate (TMPP), tetrabromobisphenol A (TBBPA), tri-n-butyl phosphate (TNBP), tri(2-butoxyethyl) phosphate (TBOEP), tris(1-chloro-2-propyl) phosphate (TCIPP), 2-ethylhexyl diphenyl phosphate (EHDPP). ToxCast results confirmed in vivo based categorization for several FRs and identified potential molecular targets. For the nine Cat I FRs, we identified several molecular targets, health outcomes and some potential AOPs. However, the complete toxicity pathways leading from molecular targets to adverse health outcomes are still unknown, with the exception of TBBPA-induced neurotoxicity.ConclusionsThe approach presented in this study was particularly useful for the categorization of a large group of replacement FRs with relatively low data availability. We highlight priority compounds that critically need more toxicological studies or FRs for which regulatory measures could be envisaged. Our research also suggests that high toxicity indicated by ToxCast is particularly relevant for predicting higher hazard in vivo. Finally, we indicate several gaps and directions for future research, such as molecular targets that could be tested in vitro and health outcomes for cohort studies. ER -
BAJARD ÉP.ESNER, Lola Murielle, Lisa Emily MELYMUK a Luděk BLÁHA. Prioritization of hazards of novel flame retardants using the mechanistic toxicology information from ToxCast and Adverse Outcome Pathways. \textit{Environmental Sciences Europe}. HEIDELBERG, GERMANY: Springer-Verlag, GmbH, Environmental Sciences Europe, 2019, roč.~31, February, s.~1-19. ISSN~2190-4715. Dostupné z: https://dx.doi.org/10.1186/s12302-019-0195-z.
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