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EC number: 934-716-8 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
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- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
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- Nanomaterial catalytic activity
- Endpoint summary
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- Biodegradation
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- Environmental data
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- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
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- Biotransformation and kinetics
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- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
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- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
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- Specific investigations
- Exposure related observations in humans
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- Additional toxicological data
Neurotoxicity
Administrative data
Description of key information
Na2S inhibited cytochrome oxidase and carbonic anhydrase prepared from brains of male rats in a concentration-dependent manner. Extensive disruption of respiratory and related mitochondrial functions was determined in homogenates of synaptosomes prepared from brains of CDI mice treated i.p. with Na2S.
Treatment of male Wistar rats with 11.7 mg/kg Na2S i.p. caused a partial inhibition of GABA and dopamine uptake, and it strongly inhibited veratridine-dependent release of these neurotransmitters and reduced veratridine-dependent changes in the trans-membrane potential in synaptosomes isolated from the hemispheres. However, single doses of Na2S (80-200 mg/kg) administered i.p. to rats indicated that very high doses are incapable of producing cerebral necrosis by a direct histotoxic effect.
Inhalation of hydrogen sulfide resulted in a marked, but reversible, decrease in the incorporation of leucine in the cerebral protein and myelin accompanied by a decreased activity of lysosomal acid proteinase after inhalation exposure of adult female mice at 100 ppm H2S for 2 h.
After repeated inhalation exposure of male rats (5 d, 3h/d) to low levels of H2S, the total power of hippocampal EEG theta activity increased in a concentration-dependent manner in both dentate gyrus and CA1 region that required two weeks for a complete recovery. Neocortical EEG and LIA (Large Amplitude Irregular Activity) were unaffected following exposure to 100 ppm H2S.
Determination of serotonin and norepinephrine levels in developing rat cerebellum and frontal cortex of pups from rats exposed for 7 h/d (GD 5 until PND 21) suggested that alterations of monoamine levels induced by H2S may produce long-lasting neurochemical changes in the CNS.
Short-term exposure of adult male rat to H2S for 3 h/d for 5 d significantly reduced motor activity, water maze performance, and body temperature following exposure to H2S concentrations ≥ 80 ppm, but did not affect regional brain catecholamine concentrations.
Key value for chemical safety assessment
Additional information
General:
As discussed in the dossier section on toxicokinetics, unrestricted read-across between the substances sodium sulfide, sodium hydrogensulfide and dihydrogen sulfide is considered feasible, in view of the potential systemic toxicity being driven by the sulfide ion as the only relevant species released from any of the sulfide substances under physiological conditions. In this context, it is further considered to be very unlikely that the sodium ions add any toxicological concern.
Read-across concept between sodium sulfide, sodium hydrogensulfide and hydrogen sulfide:
Given that sodium sulfide and sodium hydrogensulfide dissociate in aqueous media, it can safely be assumed that under most physiologically relevant conditions (i. e., neutral pH) sulfide and hydrogen sulfide anions are present at almost equimolar concentrations, thus facilitating unrestricted read-across between both species. Only under extreme conditions such as gastric juice (pH << 2), sulfides will be present predominantly in the form of the non-dissociated hydrogen sulfide. In turn, hydrogen sulfide (H2S) may be formed from both soluble sulfides, according to the following equilibria:
Na2S + H2O → NaOH + NaHS (2Na+/ OH-/ HS-)
NaHS + H2O → NaOH + H2S (Na+/ OH-/ H2S)
Similarly, hydrogen sulfide dissociates in aqueous solution to form two dissociation states involving the hydrogen sulfide anion and the sulfide anion, according to the following equilibrium:
H2S ↔ H+ + HS- ↔ 2 H+ + S2-
In conclusion, under physiological conditions, inorganic sulfides or hydrogensulfides as well as H2S will dissociate to the respective species relevant to the pH of the physiological medium, irrespective the nature of the “sulfide”, which is why read-across between these substances and H2S is considered to be feasible without any restrictions.
Results:
From mechanistic studies with intraperitoneal injection of sodium hydrogensulfide to rats it can be concluded that the lung and not the brain is the primary site of action of hydrogen sulfide, with an afferent neural signal from the lung via the vagus inducing apnea. In addition, substantial changes in neurotransmitter amino acids in the brainstem responsible for neuronal control of breathing were noted. Analyses of effects of sodium hydrogensulfide on brain transmitter systems and monoamine oxidase (MAO) activity after i.p. administration to rats led to the suggestion that inhibition of MAO may be an important contributing factor to the mechanisms underlying loss of respiratory drive after H2S exposure.
Mechanistic in-vitro and in-vivo studies with Na2S revealed that sulfide toxicity can be ascribed to the inhibition of cytochrome oxidase as key enzyme of the respiratory chain. Sodium sulfide has also been shown to strongly inhibit neuronal cytochrome oxidase and carbonic anhydrase causing disruption to respiratory and mitochondrial functions in the rat brain in vitro. Inhibitory effects on synaptosomal respiration and transmitter kinetics were shown after i.p. injection into rats with sodium sulfide.
In in-vivo studies with short-term exposures of rats to H2S, a cumulative effect on hippocampal EEG theta activity was observed at high exposure levels that required two weeks for a complete recovery. Neocortical EEG and Large Amplitude Irregular Activity (LIA) were unaffected. Furthermore, behavioural toxicity was observed in rats only at higher concentrations (≥80 ppm) of H2S. But, regional brain catecholamine levels or performance on the fixed-interval (FI) schedule were not affected. Perinatal exposure of pregnant rats to hydrogen sulfide resulted in alterations of serotonin and norepinephrine levels in the cerebellum and frontal cortex of the pups.
Justification for classification or non-classification
Based on mechanistic in-vitro and in-vivo (i.p.) studies with NaHS and Na2S, it is not possible to derive a no effect level or low effect level which is relevant for real exposure situations. This holds also true for the study with examination of effects on hippocampal EEG theta activity following short-term inhalation exposure of rats to H2S, because it cannot be ruled out that these changes are related to a sensory olfactory stimulation, and it is not known whether these changes are related to any adverse clinical effects. However, in short-term behavioural study in rats, some effects on motor activity were observed at high exposure levels. However, study duration was only 5 days, and it is likely that adaptation occurs after longer-term exposure durations, because no behavioural effects were observed in a 90-day inhalation toxicity study with H2S at the same exposure level. Although it was shown that perinatal exposure of pregnant rats to hydrogen sulfide resulted in alterations of serotonin and norepinephrine levels in the cerebellum and frontal cortex of pups, detailed behavioural tests in offspring of dams exposed by inhalation to H2S until gestation day 19 and dams and pups from postnatal day 5 to 18 revealed no clinical effects.
Therefore, it can be concluded that neurotoxicological effects of Na2S and NaHS could be demonstrated in-vitro and following i.p. injection, but subchronic inhalation exposure to H2S did not result in clinical effects of neurotoxicity in adult rats and their offspring.
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