| 1. |
- Waaijers, Susanne L., et al.
(författare)
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Persistence, Bioaccumulation, and Toxicity of Halogen-Free Flame Retardants
- 2013
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Ingår i: Reviews of Environmental Contamination and Toxicology. - New York, NY : Springer. - 9781461447160 - 9781461447177 ; , s. 1-71
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Bokkapitel (refereegranskat)abstract
- Polymers are synthetic organic materials having a high carbon and hydrogen content, which make them readily combustible. Polymers have many indoor uses and their flammability makes them a fire hazard. Therefore, flame retardants (FRs) are incorporated into these materials as a safety measure. Brominated flame retardants (BFRs), which accounted for about 21% of the total world market of FRs, have several unintended negative effects on the environment and human health. Hence, there is growing interest in finding appropriate alternative halogen-free flame retardants (HFFRs). Many of these HFFRs are marketed already, although their environ- mental behavior and toxicological properties are often only known to a limited extent, and their potential impact on the environment cannot yet be properly assessed. Therefore, we undertook this review to make an inventory of the available data that exists (up to September 2011) on the physical-chemical properties, pro- duction volumes, persistence, bioaccumulation, and toxicity (PBT) of a selection of HFFRs that are potential replacements for BFRs in polymers. Large data gaps were identified for the physical-chemical and the PBT properties of the reviewed HFFRs. Because these HFFRs are currently on the market, there is an urgent need to fill these data gaps. Enhanced transparency of methodology and data are needed to reevaluate certain test results that appear contradictory, and, if this does not provide new insights, further research should be performed. TPP has been studied quite extensively and it is clearly persistent, bioaccumulative, and toxic. So far, RDP and BDP have demonstrated low to high ecotoxicity and persistence. The compounds ATH and ZB exerted high toxicity to some species and ALPI appeared to be persistent and has low to moderate reported ecotoxicity. DOPO and MPP may be persistent, but this view is based merely on one or two studies, clearly indicating a lack of information. Many degradation studies have been performed on PER and show low persistence, with a few exceptions. Additionally, there is too l ittle information on the bioaccumulation potential of PER. APP mostly has low PBT properties; however, moderate ecotoxicity was reported in two studies. Mg(OH)₂, ZHS, and ZS do not show such remarkably high bioaccumulation or toxicity, but large data gaps exist for these compounds also. Nevertheless, we consider the latter compounds to be the most promising among alternative HFFRs. To assess whether the presently reviewed HFFRs are truly suitable alternatives, each compound should be examined individually by comparing its PBT values with those of the relevant halogenated flame retardant. Until more data are available, it remains impossible to accurately evaluate the risk of each of these compounds, including the ones that are already extensively marketed.
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| 2. |
- Fernandes, Elsa C Antunes, et al.
(författare)
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Activation and potentiation of human GABAA receptors by non-dioxin-like PCBs depends on chlorination pattern
- 2010
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 118:1, s. 183-90
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Tidskriftsartikel (refereegranskat)abstract
- The neurotoxic potential of non-dioxin-like polychlorinated biphenyls (NDL-PCBs) is characterized by disruption of presynaptic processes, including calcium homeostasis and neurotransmitter transport. Recently, using a limited set of congeners, we demonstrated that PCB28 and PCB52 can potentiate postsynaptic GABA(A) receptors. In the present study, effects of 20 NDL-PCBs and 2 dioxin-like PCBs, selected based on their chemical variation and abundance in the environment, on human GABA(A) receptors were investigated. GABA(A) receptors were expressed in Xenopus oocytes, and NDL-PCB effects were determined using the two-electrode voltage-clamp technique. Results demonstrate that lower chlorinated PCB19, PCB28, PCB47, PCB51, PCB52, PCB95, and PCB100 act as a partial agonists (at low receptor occupancy), i.e., potentiating the receptor response during coapplication with GABA (at EC(20)). Importantly, PCB19, PCB47, PCB51, and PCB100 can also act as full agonist, i.e., activate the GABA(A) receptor in the absence of GABA. Potentiation and activation of the GABA(A) receptor is concentration dependent and limited to NDL-PCBs that have 3-5 chlorine atoms, 1-3 ortho-substitutions, an equal number (0-1) of meta-substitutions on both phenyl rings, and do not have an adjacent para- and meta-substitution on the same phenyl ring. Activation and potentiation of the GABA(A) receptor by PCB47, the most potent congener (lowest observed effect concentration of 10nM), is attenuated when coapplied with PCB19, PCB28, PCB153, or PCB180, indicative for competitive binding. Considering the importance of GABA-ergic signaling for brain development, motor coordination, learning, and memory, this mode of action can contribute to the previously observed NDL-PCB-induced neurobehavioral and neurodevelopmental effects and should be included in human risk assessment.
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| 3. |
- Hendriks, Hester S., et al.
(författare)
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Effects on neonatal exposure to the flame retardant tetrabrombisphenol-A, aluminum diethylphosphinate or zinc stannate on long-term, potentiation and synaptic protein levels in mice
- 2015
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Ingår i: Archives of Toxicology. - : Springer Nature. - 0340-5761 .- 1432-0738. ; 89:12, s. 2345-2354
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Tidskriftsartikel (refereegranskat)abstract
- Brominated flame retardants such as tetrabromobisphenol-A (TBBPA) may exert (developmental) neurotoxic effects. However, data on (neuro)toxicity of halogen-free flame retardants (HFFRs) are scarce. Recent in vitro studies indicated a high neurotoxic potential for some HFFRs, e.g., zinc stannate (ZS), whereas the neurotoxic potential of other HFFRs, such as aluminum diethylphosphinate (Alpi), appears low. However, the in vivo (neuro)toxicity of these compounds is largely unknown. We therefore investigated effects of neonatal exposure to TBBPA, Alpi or ZS on synaptic plasticity in mouse hippocampus. Male C57bl/6 mice received a single oral dose of 211 µmol/kg bw TBBPA, Alpi or ZS on postnatal day (PND) 10. On PND 17–19, effects on hippocampal synaptic plasticity were investigated using ex vivo extracellular field recordings. Additionally, we measured levels of postsynaptic proteins involved in long-term potentiation (LTP) as well as flame retardant concentrations in brain, muscle and liver tissues. All three flame retardants induced minor, but insignificant, effects on LTP. Additionally, TBBPA induced a minor decrease in post-tetanic potentiation. Despite these minor effects, expression of selected synaptic proteins involved in LTP was not affected. The flame retardants could not be measured in significant amounts in the brains, suggesting low bioavailability and/or rapid elimination/metabolism. We therefore conclude that a single neonatal exposure on PND 10 to TBBPA, Alpi or ZS does affect neurodevelopment and synaptic plasticity only to a small extent in mice. Additional data, in particular on persistence, bioaccumulation and (in vivo) toxicity, following prolonged (developmental) exposure are required for further (human) risk assessment.
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| 4. |
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| 5. |
- Hendriks, Hester S., et al.
(författare)
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PCB-47, PBDE-47, and 6-OH-PBDE-47 Differentially Modulate Human GABA(A) and alpha(4)beta(2) Nicotinic Acetylcholine Receptors
- 2010
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 118:2, s. 635-642
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Tidskriftsartikel (refereegranskat)abstract
- Polychlorinated biphenyls (PCBs) and the structurally related polybrominated diphenyl ethers (PBDEs) are abundant persistent organic pollutants that exert several comparable neurotoxic effects. Importantly, hydroxylated metabolites of PCBs and PBDEs have an increased neurotoxic potency. Recently, we demonstrated that PCBs can act as (partial) agonist on GABA(A) neurotransmitter receptors, with PCB-47 being the most potent congener. It is, however, unknown whether PBDE-47 and its metabolite 6-OH-PBDE-47 exert similar effects and if these effects are limited to GABA(A) receptors only. We therefore investigated effects of PCB-47, PBDE-47, and 6-OH-PBDE-47 on the inhibitory GABA(A) and excitatory alpha(4)beta(2) nicotinic acetylcholine (nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Since human exposure is generally not limited to individual compounds, experiments with binary mixtures were also performed. The results demonstrate that PCB-47 and 6-OH-PBDE-47 act as full and partial agonist on the GABA(A) receptor. However, both congeners act as antagonist on the nACh receptor. PBDE-47 does not affect either type of receptor. Binary mixtures of PCB-47 and 6-OH-PBDE-47 induced an additive activation as well as potentiation of GABA(A) receptors, whereas this mixture resulted in an additive inhibition of nACh receptors. Binary mixtures of PBDE-47 and 6-OH-PBDE-47 yielded similar effects as 6-OH-PBDE-47 alone. These findings demonstrate that GABA(A) and nACh receptors are affected differently by PCB-47 and 6-OH-PBDE-47, with inhibitory GABA(A)-mediated signaling being potentiated and excitatory alpha(4)beta(2) nACh-mediated signaling being inhibited. Considering these opposite actions and the additive interaction of the congeners, these effects are likely to be augmented in vivo.
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