Sodium hydrogensulphide

Endpoint summary

Additional information

General read-across concept between sodium sulfide, sodium hydrogensulfide and hydrogen sulfide:

Given that sodium sulfide and sodium hydrogensulfide dissociate in aqueous media (please refer to the Hägg-graph give below), 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⁺  +  S^2-

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.

Inhalation absorption

No data on inhalation absorption are available for sodium sulfide and sodium hydrogensulfide, and little reliable information (if at all) is available on hydrogen sulfide absorption and distribution after inhalation.

Nevertheless, after completion of a testing programme on dustiness testing and particle size analysis of the airborne fraction on commercially available forms of sodium sulfide and sodium hydrogensulfide, the collected information can be used to estimate inhalation absorption factors based on a prediction of deposition patterns in the respiratory tract (MPPD model), in accordance with guidance developed under HERAG

The fate and uptake of deposited particles depends on the clearance mechanisms present in the different parts of the airway. In the head region, most material will be cleared rapidly, either by expulsion or by translocation to the gastrointestinal tract. A small fraction will be subjected to more prolonged retention, which can result in direct local absorption. More or less the same is true for the tracheobronchial region, where the largest part of the deposited material will be cleared to the pharynx (mainly by mucociliary clearance) followed by clearance to the gastrointestinal tract, and only a small fraction will be retained (ICRP, 1994). Once translocated to the gastrointestinal tract, the uptake will be in accordance with oral uptake kinetics.

In consequence, the material deposited in the head and tracheobronchial regions would be translocated to the gastrointestinal tract, where it would be subject to gastrointestinal uptake at a ratio of 100%. The material that is deposited in the pulmonary region may be assumed by default to be absorbed to 100%. This absorption value is chosen in the absence of relevant scientific data regarding alveolar absorption although knowing that this is a conservative choice. Thus, the following predicted inhalation absorption factors can be derived for sodium sulfide and sodium hydrogensulfide. For further information on particle size and dustiness, see IUCLID section 4.5.

 

Absorption factors, sodium sulfide and sodium hydrogensulfide (rounded values)

test item	absorption factors via inhalation [%]
Sodium sulfide	45
Sodium hydrogensulfide	36

 

Dermal absorption

In the absence of measured data on dermal absorption, previous guidance primarily directed at organic chemicals with a defined lipophilicity and corresponding percutaneous transfer potential, suggests the assignment of either 10% or 100% default dermal absorption rates. In contrast, the currently available scientific evidence on dermal absorption of metal cations (predominantly based on the experience from previous EU risk assessments) yields substantially lower figures, which can be summarised briefly as follows:

Measured dermal absorption values for metal cations or inorganic metal substances in studies corresponding to the most recent OECD test guidelines are typically 1 % or even less. Therefore, the use of a 10 % default absorption factor is not scientifically supported for such ionic species. This is corroborated by conclusions from previous EU risk assessments (Ni, Cd, Zn), which have derived dermal absorption rates of 2 % or far less (but with considerable methodical deviations from existing OECD methods) from liquid media.

However, considering that under industrial circumstances many applications involve handling of dry powders, substances and materials, and since dissolution is a key prerequisite for any percutaneous absorption, a factor 10 lower default absorption factor may be assigned to such “dry” scenarios where handling of the product does not entail use of aqueous or other liquid media. This approach was taken in the in the EU RA on zinc. A reasoning for this is described in detail elsewhere (Cherrie and Robertson, 1995), based on the argument that dermal uptake is dependent on the concentration of the material on the skin surface rather than it’s mass.

Consistent with the methodology proposed in HERAG guidance for metals (HERAG fact sheet - assessment of occupational dermal exposure and dermal absorption for metal cations and inorganic metal substances; EBRC Consulting GmbH / Hannover /Germany; August 2007), the following default dermal absorption factors for metal cations have therefore been proposed (reflective of full-shift exposure, i.e. 8 hours):

From exposure to liquid/wet media: 1.0 %

From dry (dust) exposure: 0.1 %

Given that the primary cause between the lack of percutaneous transfer is considered to be the ionic nature, it is proposed to assume similar behaviour for sulfides anions as for metal cations, and to adopt the above stated dermal absorption factors for sodium sulfide and sodium hydrogensulfide.

Oral absorption

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

 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). Upon distribution, sulfides 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).