Reaction mass of disodium sulphide and sodium carbonate and sodium hydrogensulphide

Endpoint summary

Description of key information

In the key study, the 90-day inhalation toxicity study with exposure of rats and mice to hydrogen sulphide (Dorman et al., 2004), no toxicologically relevant alterations in haematological indices, serum chemistries, or gross pathology. Therefore, the highest concentration of 80 ppm H2S may be considered as NOAEC for systemic effects. 
When comparing the results of the available sub-chronic studies in rats and mice, it becomes obvious that the findings of these inhalation studies are not contradictory. Brennemann et al. (2000), Moulin et al. (2002) and Dorman et al. (2004) found similar targets of toxicity. The main adverse effect caused by 30 and 80 ppm hydrogen sulphide was an exposure-related increased incidence of olfactory neuronal loss (ONL). Thus, the concentration of 10 ppm H2S represents an NOAEC for local effects in the olfactory system.

Additional information

General:

As discussed in the dossier section on toxicokinetics, unrestricted read-across between the scrubber liquid constituents sodium sulphide, sodium hydrogensulphide and dihydrogen sulphide is considered feasible, in view of the potential systemic toxicity being driven by the sulphide ion as the only relevant species released from any of the sulphide substances under physiological conditions. In this context, it is further considered to be very unlikely that the sodium ions add any toxicological concern.

An extensive literature search and evaluation programme on animal and human repeated dose toxicity data of sodium sulphide, sodium hydrogensulphide, sodium carbonate and dihydrogen sulphide has been conducted. All data sources were assessed by expert toxicologists for quality and reliability, as well as relevance for regulatory risk assessment under REACH.

Oral route:

Valid (guideline conform) data on sub-acute or sub-chronic oral toxicity for sodium hydrogensulphide or sodium sulphide in experimental animals are not available. According to the data requirements as outlined in section 8.6, column 2, Annexes VIII-IX, of Regulation (EC) 1907/2006 a repeated dose toxicity study shall be performed via the most appropriate route of administration, having regard to the likely route of human exposure. The inhalation route is considered the most appropriate route for exposure, since sodium hydrogensulfide is produced and handled only in industrial settings and the oral exposure route is not considered relevant for workers. Furthermore, the substance is not present in consumer products and is not released to the environment. The conduct of any new animal studies for repeated dose toxicity by oral route is not required.

However, in a non-reliable study (Cromwell, 1979), feeding of pigs with sodium sulphide did not affect body weight gain and the two haematological parameters measured; unfortunately, a dose-response relationship of possible other toxicologically relevant effects caused by sodium sulfide were not established. Although no effects were observed on the evaluated parameters, the information is not sufficient to establish a NOAEL. Further data on oral toxicity are not available.

Dermal route:

No reliable studies are available on dermal exposure.

According to the data requirements as outlined in Annexes VIII-IX, 8.6 column 2 of Regulation (EC) 1907/2006 a repeated dose toxicity study, dermal shall be performed via the most appropriate route of administration, having regard to the likely route of human exposure, e.g. if inhalation of the substance is unlikely; and skin contact in production and/use is likely and the physical-chemical and toxicological properties suggest potential for a significant rate of absorption through the skin. However, the inhalation route is considered as the most appropriate route of exposure for sodium hydrogensulphide, and adequate repeated dose toxicity studies are available for this route.

Taking into consideration the physico-chemical properties of sodium hydrogensulphide (especially dissociation of the highly soluble compound) and the toxicokinetic behaviour (very limited penetration into the upper epithelial layers of the epidermis) it may be concluded that there will be no systemic risks to humans with respect to dermal exposure to sodium hydrogensulfide. In addition, applying HERAG (HERAG fact sheet - assessment of occupational dermal exposure and dermal absorption for metals and inorganic metal compounds; EBRC Consulting GmbH / Hannover /Germany; August 2007) methodology, one may assume a conservative default of 1% for dermal absorption of sodium hydrogensulphide, leading to the anticipation of a negligible toxicity via the dermal route.

Sodium hydrogensulphide is not used in consumer products and due to the fact that the substance is classified as corrosive (pH 12), the workers have to use adequate gloves and protection equipment (see IUCLID section 11 “guidance on safe use”). Thus, since skin contact essentially needs to be minimised because of the protection against corrosivity, quantitatively relevant exposure and absorption through skin are not expected under conditions of normal handling and use, so that no chronic dermal toxicity study is required. Furthermore, based on the corrosive action of sodium hydrogensulphide on skin, testing on intact skin is not feasible for obvious reasons.

Inhalation route:

Since no reliable studies are available on inhalation exposure to sodium hydrogensulphide or disodium sulphide read-across from H₂S data is performed.

The 90-day inhalation study by Dorman et al. (2004) in Fischer 344 rats, Sprague-Dawley rats and B6C3F1 mice is considered to represent the most reliable study for the derivation of NOAEC values. This study, performed in conformity with GLP regulations, is considered to be of an adequate test design and quality. Different toxicological endpoints were evaluated in rats and mice of both sexes following exposure to hydrogen sulphide without signs of systemic toxicity. When comparing the results of the reliable sub-chronic studies in rats and mice, it becomes obvious that the findings of these inhalation studies are not contradictory. Brennemann et al. (2000), Moulin et al. (2002) and Dorman et al. (2004) found similar targets of toxicity.

From the key study, a NOAEC of 10 ppm H₂S (14 mg/m3 air) for local effects was derived which is based on an increased incidence of olfactory neuronal loss (ONL) at 30 and 80 ppm of hydrogen sulphide. Regarding systemic toxicity, some minor effects on food consumption and body weight were observed, but exposure did not result in toxicologically relevant alterations in haematological indices, serum chemistry, or gross pathology. Therefore, the concentration of 80 ppm H₂S (111 mg/m3 air) can be considered as NOAEC for systemic effects.

Read-across from H₂S to NaHS, Na2S and scrubber liquid:

Valid toxicological data from animal studies on sub-acute or sub-chronic inhalation exposure 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:

The soluble compound sodium hydrogensulfide (NaHS) can safely be assumed to be present dissociated in water and relevant biological media (Beauchamp et al., 1984). From sodium hydrogensulfide, hydrogen sulfide (H₂S) may be formed according to the following equilibrium:

 NaHS + H₂O    →        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⁺  +  S^2-

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 (S^2-) will be present.  

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.

 

However, because of the gaseous state of hydrogen sulfide, when drawing conclusions with respect to local effects at the olfactory system and respiratory tract, which might be generated by exposure to dust of sodium hydrogensulfide, the toxicokinetic behaviour (e.g. total absorption) of H₂S and NaHS should be taken into consideration.

Calculation of the NOAECs for both disodium sulphide and sodium hydrogensulphide were obtained by read-across to hydrogen sulphide (H₂S) data based upon their respective sulphide (S^2-) content. The sulphide content of the Scrubber Liquid was determined as 15.6%.

 

NOAEC calculation for systemic effects of scrubber liquid by read-across from H₂S:

(i)            H₂S = 34 g/mol = 111 mg/m³

(ii)           S^2-= 32 g/mol -->104.5 mg/m³

(iii)          Scrubber liquid contains 15.6 % sulphide

(v)          15.6 % = 104.5 mg/m³--> 100 % (scrubber liquid) = 670 mg/m³

Accordingly, based on read-across from the NOAEC for systemic effects of H₂S,a concentration of 670 mg/m³was derived as the NOAEC for systemic effects via inhalation to scrubber liquid.

 

 NOEAC calculation for local effects of scrubber liquid by read-across from H₂S:

(i)            H₂S = 34 g/mol = 14 mg/m³

(ii)           S^2-= 32 g/mol -->13.2 mg/m³

(iii)          Scrubber liquid contains15.6 % sulphide

(v)          15.6 % = 13.2 mg/m³--> 100 % (scrubber liquid) = 85 mg/m³

Accordingly, based on read-across from the NOAEC for local effects of H2S a concentration of 85 mg/m³was derived as a NOAEC for local effects by inhalation to scrubber liquid.

  

Human data:

No relevant human data for use in the risk assessment is available. The exposure-related observations in humans originate only from inhalation exposures to H₂S. However, read-across by extrapolation from the results of these publications on H₂S to scrubber liquid is not feasible since systemic sulphide concentrations were not reported in these references.

 

Justification for classification or non-classification

Repeated dose toxicity, oral

The currently available and reliable toxicity data on sodium hydrogensulphide, disodium sulphide or sodium carbonate or any suitable compound for read-across to NaHS does not justify classification for specific target organ toxicity - repeated exposure.

Repeated dose toxicity, dermal

(i) Based on physico-chemical properties of scrubber liquid constituents and the toxicokinetic behaviour (very limited penetration into the upper epithelial layers of the epidermis) there is no systemic risks to humans with respect to dermal exposure to scrubber liquid.

(ii) One may assume a conservative default of 1% for dermal absorption of scrubber liquid, leading to the anticipation of a negligible toxicity via the dermal route.

(ii) No risk is expected for workers due to the fact that both sodium hydrogensulphide and disodium sulphide are classified as corrosive and risk management measures are in place (worker have to use sufficient gloves and protection equipment, see IUCLID section 11 “guidance on safe use”). Thus, skin contact is unlikely and therefore absorption through skin, if any, is only possible in case of an accident.

Thus, it may be concluded that there will be no systemic risks to humans with respect to dermal exposure to scrubber liquid, and no classification for specific target organ toxicant (STOT) – repeated exposure, dermal is required.

Repeated dose toxicity, inhalation

According to regulation (EC) 1272/2008, a classification for specific target organ toxicity – repeated exposure shall be taken into account only when reliable evidence associating repeated exposure to the substance with a consistent and identifiable toxic effect demonstrates support for the classification. These adverse health effects include consistent and identifiable toxic effects in humans, or, in experimental animals, toxicologically significant changes which have affected the function or morphology of a tissue/organ, or have produced serious changes to the biochemistry or haematology of the organism and these changes are relevant for human health.

Since classification as corrosive to respiratory tract is proposed for both sodium sulphide and sodium hydrogensulphide, and for the reasons presented below, no classification for specific target organ toxicant (STOT) – repeated exposure, inhalation is required for scrubber liquid.

The following observations have been made in experimental animal studies with hydrogen sulfide (read-across):

(i) No systemic toxicity was shown to result from subchronic inhalation exposure in rats or mice to concentrations of hydrogen sulphide up to 80 ppm (NOAEC_systemicH₂S). Some minor effects on food consumption and body weight were observed, but exposure did not result in toxicologically relevant alterations in haematological indices, serum chemistry, or gross pathology.

(ii) From the key study, a NOAEC of 10 ppm H₂S (14 mg/m³air) for local effects was derived which is based on an increased incidence of olfactory neuronal loss (ONL) at 30 and 80 ppm of hydrogen sulfide.

According to the CLP regulation, classification is required for significant toxic effects and thus, it should be based on an effect level at which significant and severe effects are observed. Based on the results presented in the publication (Dorman 2004), it can be argued that significant and severe effects are observed only at 80 ppm, but not at 10 and 30 ppm. In rats at 30 ppm, the severity grade and extent of lesions is in principle mild. In addition, taking the argumentation into consideration that these local effects can be considered as rat specific, it appears appropriate to select the 80 ppm exposure concentration as a clear effect level. 80 ppm H₂S corresponds to 111.5 mg/m³or 0.112 mg/l H₂S. Recalculation to scrubber liquid results in 0.67 mg/l.

Based on this argumentation the level is > 0.2 mg/l for scrubber liquid and classification with STOT RE Cat 2 would not be required.