Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

See discussion below.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
100
Absorption rate - inhalation (%):
100

Additional information

Justification for read across

The derivation of the DNELs is based on read across to other sulfur based substances. Toxicological data specifically for Sodium sulfide (Na2(Sx)) from animal studies are not available. Therefore, because of the lack of appropriate experimental data, read-across from studies with H2S is proposed based on the following reasoning:

                    

Unrestricted read-across between the substances Sodium sulfide (Na2(Sx)), 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.

 

Aqueous Na2Sx solutions are only stable at pH > 10. At lower pH values they are decomposed to H2S and S ([1, 2, 3, 4, 5])

 

The soluble compound Sodium sulfide (Na2(Sx)) can safely be assumed to be present dissociated in water and relevant biological media([6]). From Sodium sulfide (Na2(Sx)), hydrogen sulfide (H2S) may be formed according to the following equilibria:

Na2Sx+ H2O → NaOH + NaHSx(2 Na++ HSx-+ OH-)

NaHSx +H2O → (x-1)S + NaOH + H2S (Na++ OH-+ H2S)

The toxic effects resulting from the sodium ion is negligible. Hydrogen sulfide dissociates in aqueous solution to form two dissociation states involving the hydrogen sulfide anion and the sulfide anion:

H2S ↔ H++ HS-↔ 2 H++ S2-

The pKa values for the first and second dissociation steps of H2S are 7.04 and 11.96, respectively. Therefore, at physiological pH values, hydrogen sulfide in the non-dissociated form (H2S) and the hydrogen sulfide anion (HS-) will be present in almost equimolar proportion, whereas only very small amounts of the sulfide anion (S2-) will be present. In conclusion, under physiological conditions, inorganic sulfides or hydrogen sulfides 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.

 

[1] E. Dachselt, „Thioplaste“, Deutscher Verlag für Grundstoffindustrie, Leipzig 1971, pp. 35

[2] M.B. Berenbaum, “Polysulfide Polymers” in N. G. Gaylord, ”Polyethers”, Interscience Publishers, 1962, 49-51

[3] D. Peschanski; G. Valensi, J. chim.Phys. 46(1949), pp. 602

[4] M. Menzel, Expert statement “Investigation of the reaction of sodium polysulfide solution with diluted hydrochlorioc acid”, AkzoNobel, Greiz (March 2010) (attached)

[5] Hagg-graph (attached)

[6]Beauchamp et al. (1984): A critical review of the literature on hydrogen sulfide toxicity; CRC Crit. Rev. Toxicol. 13, 25-97. (attached)

 

Toxicokinetics, metabolism and distribution

Soluble sulfides are reported to be rapidly and completely hydrolyzed in body fluids to produce hydrogen sulfide. As a result, there are no toxicological distinctions between them and hydrogen sulfide in terms of their systemic effects and toxicokinetic profile (Health Canada 1987).

 

"Hydrogen sulfide is produced endogenously as part of normal biological function, playing a role in regulating blood pressure, body temperature, vascular smooth muscle, cardiac function and cerebral ischemia and in modulating the hypothalamic–pituitary– adrenal axis. It is produced by the brain, liver, heart and gastrointestinal tract (Kimura 2002; Kamoun 2004; Linden et al. 2010). Endogenous hydrogen sulfide is produced from cysteine by cystathionine β-synthase and cystathionine γ-lyase (Abe and Kimura 1996; Lu et al. 2008). In the brain, the endogenous levels of hydrogen sulfide detected range from 50 to 160 μM in humans, rats and bovines (Abe and Kimura 1996; Lu et al. 2008). Hydrogen sulfide in the gastrointestinal system has also been attributed to the metabolism of sulfhydryl-containing amino acids by bacteria present in the intestinal tract and the mouth (Abe and Kimura 1996)."(From Health Canada 2017)

Inhalation absorption

No data on inhalation absorption are available for sodium sulfide (Na(Sx)) or its read across substances: sodium sulfide, sodium hydrogensulfide, and little reliable information (if at all) is available on hydrogen sulfide absorption and distribution after inhalation.

The material may be assumed by default to be absorbed to 100%. This absorption value is chosen in the absence of relevant scientific data regarding absorption although knowing that this is a conservative choice.

 

Dermal absorption

No data on dermal absorption are available for sodium sulfide (Na(Sx)) or its read across substances: sodium sulfide, sodium hydrogensulfide, and hydrogen.

The material may be assumed by default to be absorbed to 100%. This absorption value is chosen in the absence of relevant scientific data regarding absorption although knowing that this is a conservative choice.

 

Oral absorption

No data on oral absorption are available for sodium sulfide (Na(Sx)). There are only few publications that allow an assessment of the oral bioavailability of sodium sulfide in rats, which are also somewhat of age. Nevertheless, the following conclusions can be drawn: after oral administration of sulfide to rats (Curtis et al., 1972) almost 70% are excreted within 48 hrs, 63% via urine and the remainder via faeces. In another study involving i.p.-administration, 90% of the injected dose could be recovered in urine and faeces (Dziewiatkowski, 1945). In conclusion, the assumption appears justified that upon oral uptake the systemic uptake is essentially complete for sulfides and hydrogen sulfides. Therefore, a conservative oral absorption factor of 100% will be taken forward for risk characterisation purposes.

   

Distribution, metabolism and elimination

No data are available for sodium sulfide (Na(Sx)). Following oral administration, sulfides are absorbed rapidly and extensively, and distributed widely throughout all tissues without any particular target tissue (Curtis et al., 1972; Dziewiatkowski, 1945; Nagata et al., 1994). Upon distribution, sulfide is rapidly excreted as sulfate with thiosulfate having been identified as an intermediate metabolite (Bartholomew et al.,1980). The resulting sulfate is excreted almost quantitatively via urine; experiments with bile duct cannulated rats have shown that biliary excretion is minimal by comparison (Curtis et al., 1972). Methylation with subsequent elimination via exhaled air has been excluded for sulfides (Susman et al., 1978).