Sodium hydrogensulphide

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study is reliable with restrictions. Deficiencies are low animal number per dose group, purity of the test substance not stated, no PCE/NCE ratio given, and no toxic effects reported. However, due to the well reported test, the test institution with established reputation, and the publication in a peer-reviewed high quality journal the data is rated as reliable. Furthermore LD50 values for the test substance could be retrieved from other adequate acute toxicity studies.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1981

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Test performed according to: Schmid, W.: The micronucleus test for cytogenic analysis, in: A. Hollaender (Ed.), Chemical Mutagens, Vol. 4, 1976, 31-53.

Deviations:

not specified

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

, low animal number per dose group, purity of the test substance not stated, no PCE/NCE ratio given, and no toxic effects reported

GLP compliance:

not specified

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Disodium sulphide

EC Number:

215-211-5

EC Name:

Disodium sulphide

Cas Number:

1313-82-2

Molecular formula:

Na2S

IUPAC Name:

disodium sulfide

Details on test material:

- Name of test material (as cited in study report): Sodium sulfide
- Substance type: technical product
- Physical state: solid
- Test substance supplier: Merck Co., Darmstadt
No further details are given.

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Mice were obtained from S. Ivanovas GmbH and Co., KIsslegg/Allgäu (Germany).
- Diet: ad libitum, standard chow
- Water: ad libitum
No further details are given.

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: 0.375M phosphate buffer, pH 7.2

Details on exposure:

Animals treated at 0 and 24 h, bone-marrow smears prepared at 30 h

Duration of treatment / exposure:

30 hours

Frequency of treatment:

The animals were treated at 0 and 24 hours.

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
96.1 mg/kg
Basis:
nominal conc.
test material Na2S

Doses / concentrations 2

Remarks:

Doses / Concentrations:
48.0 mg/kg
Basis:
nominal conc.
test material Na2S

Doses / concentrations 3

Remarks:

Doses / Concentrations:
24.0 mg/kg
Basis:
nominal conc.
test material Na2S

No. of animals per sex per dose:

4 mice (2 male and 2 female animals) were used for each dose.

Control animals:

yes

Positive control(s):

Pyrogallol, i.p.

Examinations

Tissues and cell types examined:

After 30 hours bone marrow smears were prepared.

Details of tissue and slide preparation:

Slides were coded and 1000 polychromatic erythrocytes were scored per mouse.

Statistics:

Significance was calculated according to the Kastenbaum-Bowman tables.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

One animal died in the 24 mg/kg dose-group.

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

not examined

Additional information on results:

Dose, MN PCE(%), Survival
0.0 mg/kg: 1.9, 4/4
24.0 mg/kg: 2.9, 3/4
48.0 mg/kg: 1.9, 4/4
96.1 mg/kg: 1.8, 4/4

-Positive control increased MN PCE ratio significantly and dose-dependent (low dose 3,8%, mid dose 14.7%, high dose 25.4%)
-No further toxic effects reported
-No PCE/NCE ratio given

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative No significant exerted mutagenic action was observed.
No significant exerted mutagenic action was observed.

Executive summary:

Read-across from Na₂S to NaHS:

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⁺  +  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.