Reaction mass of disodium sulphide and sodium hydrogensulphide

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity

Remarks:

acute

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well-documented paper to be considered as supplementary information on the mechanism of sulfide toxicity

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Sulfide toxicity: mechanical ventilation and hypotension determine survival rate and brain necrosis.

Author:

Baldelli, R.J.

Year:

1993

Bibliographic source:

J. Appl. Physiol. 75, 1348-1353

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Ventilated and unventilated rats were studied to allow administration of higher doses of sulfide and to facilitate physiological monitoring. Single doses (80-200 mg/kg) were administered intraperitoneal. After one week the animals' brains were removed and processed histologically.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1313-84-4

Cas Number:

1313-84-4

IUPAC Name:

1313-84-4

Constituent 2

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

Constituent 3

Reference substance name:

disodium sulfide nonahydrate

IUPAC Name:

disodium sulfide nonahydrate

Details on test material:

- Name of test material (as cited in study report): sulfide
- Molecular formula (if other than submission substance): Na2S*9H2O
- Molecular weight (if other than submission substance): 240.18 g7mol
- Substance type: technical product
- Physical state: solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

physiological saline

Details on exposure:

The stock solution was prepared from Na2S*9H2O dissolved in 0.9 % NaCl.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Single administration, observation period of 1 week

Frequency of treatment:

Once

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
84, 96, 100, 108, 120 and 200 mg/kg bw (unventilated groups)
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
120, 150, and 200 mg/kg bw (ventilated groups)
Basis:
nominal conc.

No. of animals per sex per dose:

Unventilated groups: 32 animals (total)
Ventilated groups: 14 animals (total)

Control animals:

not specified

Examinations

Observations and clinical examinations performed and frequency:

Survivors were observed for 1 week after treatment.

Sacrifice and (histo)pathology:

After one week the animals' brains were removed and processed for histological examination.

Results and discussion

Results of examinations

Details on results:

CLINICAL SIGNS AND MORTALITY
Unventilated group:
- NaS2 was lethal in 24 of 32 animals. Mean time to death was 5:50 +/- 0:23 min.
- All 11 animals receiving >120 mg/kg died in less than 10 min of neurogenic apnea.
- 7 out of 10 died at 120 mg/kg. 3 out of 3 died at 108 mg/kg, 1 out of 2 died at 100 mg/kg, 2 out of 5 at 96 mg/kg and 1 of 1 at 84 mg/kg.
- The clinical effects of increasing doses of NaS2 progressed through 4 levels in the following sequence: 1) behavioural effects, 2) convulsions, 3) loss of consciousness, 4) death (<10 min) due to cardiorespiratory inhibition and asphyxiation.
- Pulmonary congestion and oedema was seen in all animals.
- One unventilated rat at 120 mg/kg showed neural necrosis in the cerebral cortex.

NEUROTOXICITY
- Only 1 of 8 surviving unventilated rats given high-doses of sulfide (a dose that was lethal in > 50% of animals) showed cerebral necrosis.
- Mechanical ventilation shifted the dose that was lethal in 50% of the animals to 190 mg/kg bw from 94 mg/kg bw in the unventilated rats.
- Cerebral necrosis was absent in the ventilated rats. Sulfide was found to potently depress blood pressure in ventilated animals.

Effect levels

Dose descriptor:

NOAEL

Basis for effect level:

other: The authors concluded that very-high-dose sulfide is incapable of producing cerebral necrosis by a direct histotoxic effect.

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Applicant's summary and conclusion

Conclusions:

No NOEAL could be derived from this study. The authors concluded that very-high-dose sulfide is incapable of producing cerebral necrosis by a direct histotoxic effect.