Disodium sulphide

Endpoint summary

Description of key information

Acute oral toxicity: Acute oral toxicity of sodium sulfide is assessed using a weight-of-evidence approach. Two reliable studies (RL=1) with Na2S were included. An LD50 of 254 mg/kg bw could be derived for sodium sulfide (60 %) from the Ullmann (1986) study report. The result indicates that the LD50 calculated for the most concentrated commercial form Na2S, 62 %, would be 246 mg/kg bw. Second, an LD50 of 1122 mg/kg bw was calculated for sodium sulfide (anhydrous) in the study by Mason (1998). The result indicates that the LD50 calculated for the most concentrated commercial form Na2S, 62 %, would be 1810 mg/kg bw. Based on a comparison with sodium hydrogensulfide as an analogous substance, the lower LD50 value will be used for classification.
Acute inhalation toxicity: no reliable studies available, but minimal risk of inhalation concluded.
Acute dermal toxicity: No reliable studies available; the Seaman (1982) study (RL=3), despite being regarded as clearly invalid, is reported since the current legal classification is based on this study result (LD50<340 mg/kg bw).

Additional information

General

A literature search and evaluation programme on animal and human acute toxicity data of sodium sulfide 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. The results are attached to the technical dossier in a tabular report (IUCLID section 13).

Acute oral toxicity:

For sodium sulfide, two reliable acute oral toxicity studies (RL=1, Ullmann_1986 and Mason_1998) are available. However, the resulting LD50 values vary markedly (factor seven) between both studies:

Ullmann_1986: LD50 =254 mg/kg bw for Na₂S (ca. 60 %)
->the LD50calculated for the most concentrated commercial form Na₂S, 62 %,would be 246 mg/kg bw.

Mason_1998: LD50 = 1122 mg/kg bw for Na₂S (anhydrous)
-->the LD50calculated for the most concentrated commercial form Na₂S, 62 %,would be 1810 mg/kg bw.

Despite yielding a “borderline” result, the Ullmann-study would formally lead to a classification as “toxic if swallowed” according to the criteria specified by Directive 67/548/EC, Regulation (EC) No 1272/2008 and subsequent regulations. In contrast, the Mason-study would merely lead to a classification as “harmful if swallowed” according to the criteria specified by Directive 67/548/EC, Regulation (EC) No 1272/2008 and subsequent regulations.

For clarification of this seeming discrepancy, read-across to sodium hydrogensulfide as an analogous substance is made: there, two reliable studies exist which however both yield an LD50 < 250 mg/kg bw, thus necessitating a classification as “toxic if swallowed“. Thus, by applying a weight-of-evidence approach, it is proposed to use the lower LD50 value of the commercial form (246 mg/kg for Na₂S, 62 %) from the Ullmann (1986) study report for a more conservative classification of the substance.

 

Acute inhalation toxicity:

No reliable data are available for acute inhalation toxicity of sodium sulfide. Although this is a potential route of exposure for workers, testing is not justified since the test substance is classified as corrosive to skin and has a pH value >=11.5. Therefore, in accordance with section 8.5.2, column 2 Annex VIII of Regulation (EC) 1907/2006, in-vivo testing for acute toxicity study via inhalation does not need to be conducted. In addition, sodium sulfide is marketed as a solid, coarse flaky product of low dustiness with a very low percentage of fine material. In detailed particle size distribution analyses of the commercial product, it could clearly be shown that the potential to generate an inhalable atmosphere is indeed very low, with a concurrent absence of risk of inhalation of any relevant amount of the substance (see summary, section 7.1).

Acute dermal toxicity:

In the study report on acute dermal toxicity of sodium sulfide (60 % flakes) by Seaman,1982 [cited in IUCLID (2000) as TSCATS Accession number 26523, NTIS/OTS 505455, EPA doc N° 88-8100368, (1982) ], rabbits were treated with the test material at a dose level of 340 mg/kg bw, after which 9/10 animals died. However, the test material was applied toabradedskin (involving a series of scratches by which the stratum corneum was penetrated/abraded with a gauge needle), instead of intact skin. The study was assessed for relevance and reliability for risk assessment according to the criteria proposed by Klimisch et al. (1997), with the following conclusion: the study was rated as not reliable (RL=3) for use in EU risk assessment. The primary reason for this was that according to guideline OECD 402 (1987), care must be taken to avoid abrading the skin, which would alter its permeability, implying that the LD50 should be determined for animals treated via intact skin. Since the skin was damaged on purpose in this study by prior abrasion, the mandatory prerogative of an intact skin surface is violated.

In conclusion, reliable and relevant data on acute dermal toxicity of sodium sulfide are not available. Although this is a potential route of exposure for workers, new testing is not justified for animal welfare grounds: in accordance with section 8.5.3, column 2, Annex VIII of Regulation (EC) No. 1907/2006, an in-vivo acute dermal toxicity study does not need to be conducted since the test substance is classified as corrosive to skin (sodium sulfide has a pH value ≥11.5 in aqueous solution).

 

 

Justification for classification or non-classification

Acute oral toxicity:

There are two reliable studies for acute oral toxicity testing with Na₂S (Ullman_1986 and Mason_1998), yielding LD50 values of 246 mg/kg bw and 1810 mg/kg bw, respectively. Based on a comparison of these data with similar data for the analogous substance sodium hydrogensulfide, it is proposed by applying a weight-of-evidence approach to use the lower LD50 value calculated for the commercial form (246 mg/kg for Na₂S, 62 %) from the Ullmann (1986) study report, for a more conservative classification of the substance.

Thus, the current harmonised classification of sodium sulfide as “harmful if swallowed” according to “Commission Regulation (EC) No 790/2009: (1. ATP of Regulation No 1272/2008)”, Annex I and Annex IV: List of harmonised classification and labelling of hazardous substances in Regulation No 1272/2008, should not be adopted. Instead, it is proposed to classify the substance more conservatively as “toxic if swallowed”.

Specific target organ toxicant (STOT) – single exposure: oral

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met. No additional classification required.

 

Acute inhalation toxicity:

No classification is proposed for acute inhalation toxicity in the absence of an appropriate study. According to the data requirements as outlined in section 8.5, Annexes VII-VIII of Regulation (EC) 1907/2006 no new testing should be conducted as the substance is classified as skin corrosive cat.1b (causes severe skin burns and eye damage) according to Regulation (EC) No 1272/200.

 

Acute dermal toxicity:

Current classification:Annex 1 of 1. ATP of the CLP Regulation [Commission Regulation (EC) No 790/2009 of 10 August 2009 amending, for the purposes of its adaptation to technical and scientific progress, Regulation (EC) No 1272/2008 of the European Parliament and of the Council on classification, labelling and packaging of substances and mixtures], Index No. 016-009-00-8, includes a classification as “H311: Toxic in contact with skin” for sodium sulfide (Annex IV includes a classification as R24). This classification does not appear in the previous versions of the “CLP Regulation” [Regulation (EC) No 1272/2008].

According to ECBI/90/06 Rev.8, chapter 11.3: Revision of the classification for acute toxicity for some Annex I entries based on new data, “ECB informed that BE proposed to update the acute toxicity of 4 substances[...]”. “BE said that they were approached by IND to update these Annex I entries in accordance with existing data for acute toxicity[...]”. “Further during the follow-up period TC C&L also agreed to update the classification of Sodium sulfide (Index No: 016-009-00-8, CAS No: 1313-82-2, EC No: 215-211-5) with T; R24 – Xn; R22 – R31 – C; R34- N; R50 [... ])”. In summary, Belgium proposed to make a new entry in Annex I for classification of sodium sulfide as toxic in contact with skin at the “Meeting on Health Effects of Pesticides, Biocides, Existing Chemical, New Chemicals and General issues” in March 2006. The Belgian proposal is documented in ECBI/41/06 which describes the study on which the proposal was based. The study which serves as basis for this classification (T; R24) of sodium sulfide is the study cited in IUCLID (2000): TSCATS Accession number 26523, NTIS/OTS 505455, EPA doc N° 88-8100368, (1982). This is the reference "Seaman, L. R. (1982): Acute dermal toxicity study - sodium sulfide, 60 % Flake. FMC Toxicology Laboratory, 76 Fourth Street, Somerville, New Jersey, 08876, U. S. A. Report No.: I81-522", described in IUCLID section 7.2.3 Acute toxicity: dermal: d_Seaman_1982.

Study description and evaluation:In the above mentioned study report on acute dermal toxicity of sodium sulfide (60 % flakes) by Seaman,1982 [cited in IUCLID (2000) as TSCATS Accession number 26523, NTIS/OTS 505455, EPA doc N° 88-8100368, (1982) ], rabbits were treated with the test material at a dose level of 340 mg/kg bw, after which 9/10 animals died. Furthermore, it was observed that the test material was highly corrosive to the skin. However, the test material was applied toabradedskin (involving a series of scratches by which the stratum corneum was penetrated/abraded with a gauge needle), instead of intact skin.

The study was assessed for relevance and reliability for risk assessment according to the criteria proposed by Klimisch et al. (1997), with the following conclusion: the study was rated as not reliable (RL=3) for use in EU risk assessment. The primary reason for this was that according to guideline OECD 402 (1987), care must be taken to avoid abrading the skin, which would alter its permeability, implying that the LD50 should be determined for animals treated via intact skin. Since the skin was damaged on purpose in this study by prior abrasion, the mandatory prerogative of an intact skin surface is violated.

No other reliable and relevant data on acute dermal toxicity of sodium sulfide are available. Although this is a potential route of exposure for workers, new testing is not justified for animal welfare grounds: in accordance with section 8.5.3, column 2, Annex VIII of Regulation (EC) No. 1907/2006, an in-vivo acute dermal toxicity study does not need to be conducted, since the test substance is classified as corrosive to skin (sodium sulfide has a pH value ≥11.5 in aqueous solution).

Conclusions:Since the study described above is considered not reliable and unsuitable for the assessment of acute dermal toxicity of sodium sulfide, the classification as “toxic in contact with skin” is unjustified and incorrect. It is therefore proposed to correct the classification of sodium sulfide according to the evaluation results based on current assessment criteria for study reports by deleting the classification H311 from Annex I and R24 from Annex IV of Commission Regulation (EC) No 790/200 und subsequent regulations.