Registration Dossier

Toxicological information

Neurotoxicity

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Description of key information

The following information is available for neurotoxicity potential of the registered substance:
Mariussen, E. and Fonnum, F. (2003). The effect of brominated flame retardants on neurotransmitter uptake into rat brain synaptosomes and vesicles. Neurochemistry International (2003), Vol. 43, pp.533-542.
Reistad, T., Fonnum, F. and Mariussen, E. (2006). Neurotoxicity of the pentabrominated diphenyl ether mixture, DE-71, and hexabromocyclododecane (HBCD) in rat cerebellar granule cells in vitro. Arch. Toxicol. (2006), Vol. 80, pp.785-795.
It was not possible to score either neurotoxicity studies for reliability due to non-standard methodologies and lack of reporting of scientific principles. The studies were therefore both awarded reliability scores of 4 according to the criteria of Klimisch et al. (1997). It should be noted that the concentrations used in those assays are far above the water solubility of HBCDD and probably yhe solubility in the media. In vitro studies under those conditions are of questionable value and no conclusion can be drawn from those experiments.

Key value for chemical safety assessment

Additional information

Mariussen et al. (2003) conducted several experiments to evaluate the effect of brominated flame retardants, including the registered substance, on neurotransmitter uptake in rat brain synaptosomes and vesicles. Original test methodologies were used to model the effect of the registered substance on the rat brain, which makes comparing the investigations carried out by Mariussen et al. (2003) to other investigations difficult. Mariussen et al. (2003) reported that the registered substance inhibited the uptake of dopamine (IC50 4±1µm) and Glutamate (IC50 26±9µm) in rat synaptosomes and partly inhibited TPP+ uptake in rat synaptosomes under the conditions of the test. Mariussen et al. (2003) also reported that the registered substance induced the death of CGC in low micromolar concentrations.

Reistad et al. (2006) also examined the effect of the registered substance on vesicular uptake of dopamine in the rat brain, however, the methodology differed significantly from that employed by Mariussen et al. (2003). Reistad et al. (2006) concluded that the registered substance inhibited dopamine uptake in the rat brain and reported an IC50 value of 3±1µm.

Justification for classification or non-classification

No classification for neurotoxicity or adverse effect upon the central nervous system has been placed upon the registered substance. The available data do not indicate any specific target organ toxicity at relevant dose levels. In vitro data are not of a quality that they can be used in an assessment of the human health effects of the substance. They are also of limited use for considerations on a mode of action.