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Toxicological information

Neurotoxicity

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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

Constituent 1
Reference substance name:
1313-84-4
Cas Number:
1313-84-4
IUPAC Name:
1313-84-4
Constituent 2
Chemical structure
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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
84, 96, 100, 108, 120 and 200 mg/kg bw (unventilated groups)
Basis:
nominal conc.
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.