TY - JOUR
T1 - A comparison of the in vitro cyto- and neurotoxicity of brominated and halogen-free flame retardants: prioritization in search for safe(r) alternatives
T2 - Prioritization in search for safe(r) alternatives
AU - Hendriks, Hester S.
AU - Meijer, Marieke
AU - Muilwijk, Mirthe
AU - van den Berg, Martin
AU - Westerink, Remco H. S.
PY - 2014/4
Y1 - 2014/4
N2 - Brominated flame retardants (BFRs) are abundant persistent organic pollutants with well-studied toxicity. The toxicological and ecological concerns associated with BFRs argue for replacement by safe(r) alternatives. Though previous research identified the nervous system as a sensitive target organ for BFRs, the (neuro) toxic potential of alternative halogen-free flame retardants (HFFRs) is largely unknown. We therefore investigated the in vitro (neuro) toxicity of 13 HFFRs and three BFRs in dopaminergic pheochromocytoma (PC12) and neuroblastoma (B35) cells by assessing several cytotoxic and neurotoxic endpoints. Effects on cell viability and production of reactive oxygen species (ROS) were measured using a combined Alamar Blue and Neutral Red assay and a H-2-DCFDA assay, respectively, whereas effects on calcium homeostasis were measured using single-cell fluorescent Ca2+-imaging. The majority of the tested flame retardants induced negligible cytotoxicity, except zinc hydroxystannate (ZHS) and zinc stannate (ZS). A considerable fraction of flame retardants affected ROS production (decabromodiphenyl ether (BDE-209), triphenylphosphate (TPP), aluminium trihydroxide (ATH), ammonium polyphosphate (APP), magnesium hydroxide (MHO), ZHS, ZS and melamine polyphosphate (MPP)). Interestingly, ATH, ZHS, ZS and montmorillonite (MMT) increased the basal intracellular calcium concentration ([Ca2+](i)), whereas tetrabromobisphenol A (TBBPA), resorcinol bis (diphenylphosphate) (RDP), TPP, 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO), ATH, ZHS, ZS and MMT reduced depolarization-evoked increases in [Ca2+](i) as a result of inhibition of voltage-gated calcium channels. These combined data on the in vitro (neuro) toxicity of HFFRs in comparison with BFRs are essential for prioritization of safe(r) flame retardants. Though additional data are required for a complete (toxic) risk assessment, our data demonstrate that several HFFRs could be suitable substitutes for BFRs
AB - Brominated flame retardants (BFRs) are abundant persistent organic pollutants with well-studied toxicity. The toxicological and ecological concerns associated with BFRs argue for replacement by safe(r) alternatives. Though previous research identified the nervous system as a sensitive target organ for BFRs, the (neuro) toxic potential of alternative halogen-free flame retardants (HFFRs) is largely unknown. We therefore investigated the in vitro (neuro) toxicity of 13 HFFRs and three BFRs in dopaminergic pheochromocytoma (PC12) and neuroblastoma (B35) cells by assessing several cytotoxic and neurotoxic endpoints. Effects on cell viability and production of reactive oxygen species (ROS) were measured using a combined Alamar Blue and Neutral Red assay and a H-2-DCFDA assay, respectively, whereas effects on calcium homeostasis were measured using single-cell fluorescent Ca2+-imaging. The majority of the tested flame retardants induced negligible cytotoxicity, except zinc hydroxystannate (ZHS) and zinc stannate (ZS). A considerable fraction of flame retardants affected ROS production (decabromodiphenyl ether (BDE-209), triphenylphosphate (TPP), aluminium trihydroxide (ATH), ammonium polyphosphate (APP), magnesium hydroxide (MHO), ZHS, ZS and melamine polyphosphate (MPP)). Interestingly, ATH, ZHS, ZS and montmorillonite (MMT) increased the basal intracellular calcium concentration ([Ca2+](i)), whereas tetrabromobisphenol A (TBBPA), resorcinol bis (diphenylphosphate) (RDP), TPP, 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO), ATH, ZHS, ZS and MMT reduced depolarization-evoked increases in [Ca2+](i) as a result of inhibition of voltage-gated calcium channels. These combined data on the in vitro (neuro) toxicity of HFFRs in comparison with BFRs are essential for prioritization of safe(r) flame retardants. Though additional data are required for a complete (toxic) risk assessment, our data demonstrate that several HFFRs could be suitable substitutes for BFRs
KW - Brominated flame retardants (BFRs)
KW - Halogen-free flame retardants (HFFRs)
KW - In vitro neurotoxicology
KW - Prioritization
KW - Risk assessment
KW - Substitution of BFRs
UR - http://www.scopus.com/inward/record.url?scp=84897113604&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00204-013-1187-1
DO - https://doi.org/10.1007/s00204-013-1187-1
M3 - Article
C2 - 24395120
SN - 0340-5761
VL - 88
SP - 857
EP - 869
JO - Archives of Toxicology
JF - Archives of Toxicology
IS - 4
ER -