Reaction mass of disodium sulphide and sodium hydrogensulphide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

1986-08-21 to 1986-09-29

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Comparable to guideline without restrictions. Only minor deviations with no effect on the study: - The stability of the test substance was not stated. - 20 ml of 5000 mg/kg was administered, while a volume of 10 ml was administered of all other dose levels. - The findings for 5000 mg/kg were not used for determining the LD50 estimate. - According to the guideline, changes in weight should be calculated and recorded when survival exceeded one day. This is missing in this report. However body weight data are available. - According to the guideline, the number of animals showing toxic signs other than mortality should be stated. This was missing in the report.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 1981

Deviations:

yes

Remarks:

see rational for reliability

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

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

Constituent 2

Reference substance name:

sodium sulfide (60 %)

IUPAC Name:

sodium sulfide (60 %)

Details on test material:

- Name of test material (as cited in study report): Schwefelnatrium Schuppen 60 %
- Substance type: technical product
- Physical state: solid
- Other: The test substance is assumed to be the hydrated form of sodium sulfide (see reference substance).
No further information on the test material was stated.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellingdorf /Switzerland
- Age at study initiation: 9 to 14 weeks
- Weight at study initiation: Males: 188 - 237 g; females: 169 - 210 g
- Fasting period before study: 12 to 18 hours (access to water was not interrupted). Food was again presented approx. one hour after dosing.
- Housing: Groups of five in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schwill AG, 4132 Muttenz, Switzerland)
- Diet (ad libitum): Pelleted standard Kliba 343, Batch 50/86 rat maintenance diet ("Kliba", Klingentalmuehle AG, 4303 Kaiseraugst, Switzerland)
- Water (ad libitum): Community tap water from Itingen
- Acclimation period: At least six days under laboratory conditions, after veterinary examination


ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Relative humidity: 40 - 70 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Test article preparation:
The test article was placed into a glass beaker on a tared Mettler PK 4800 balance, and the vehicle (distilled water) was added. A weight by volume dilution was prepared using a homogenizer (Ultra-Turrax, Janke and Kunkel, Staufen, FRG)
Homogeneity of the test article in the vehicle was maintained during treatment using a magnetic stirrer (Auer_Bittmann, 8953 Dietikon, Switzerland). The preparation was made immediately prior to dosing.

MAXIMUM DOSE VOLUME APPLIED: 20 ml (only for the dose level 5000 mg/kg; 10 ml was used for the other dose levels)
No further information on details on oral exposure was stated.

Doses:

50 mg/kg, 150 mg/kg, 500 mg/kg, 5000 mg/kg (only males)

No. of animals per sex per dose:

5 males / 5 females

Control animals:

not specified

Details on study design:

- Duration of observation period following administration:15 days
- Frequency of observations and weighing: Mortality/Viability was checked four times during test day 1, and daily during day 2-15. The body weight was determined on test days 1 (pre-administration), 8 and 15. Each animal was examined for changes in appearance and behaviour four times during day 1, and daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: Yes, all animals were necropsied. All animals surviving to the end of the observation period were killed by intraperitoneal injection of sodium pentobarbitone.
No further information on details on study design were given.

Statistics:

The LOGIT-Model (COX, Analysis of Binary Data, London 1977) was applied to estimate the toxicity value. Additionally, the 90, 95 and 99% confidence intervals for the toxicity for each sex and the slope of the dose response line were estimated.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

253.8 mg/kg bw

Based on:

test mat.

Remarks:

Na2S, 60 %

95% CL:

162.1 - 483.3

Remarks on result:

other: The results indicate that the LD50 (male and female) calculated for the most concentrated commercial form Na2S, 62 %, would be 246 mg/kg bw.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

264 mg/kg bw

Based on:

test mat.

Remarks:

Na2S, 60 %

95% CL:

118.6 - 2 165

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

226.8 mg/kg bw

Based on:

test mat.

Remarks:

Na2S, 60 %

95% CL:

117 - 824.7

Mortality:

Number of dead males per dose:
50 mg/kg: 0/5
150 mg/kg: 1/5 (1 hour after the start of experiment)
500 mg/kg: 4/5 (1 hour after the start of experiment)
5000 mg/kg: 5/5 (1 minute after application)
Number of dead females per dose:
50 mg/kg: 0/5
150 mg/kg: 0/5
500 mg/kg: 5/5 (4 females 1 hour after the start of experiment; 1 females 2 hours after the start of experiment)

Clinical signs:

Clinical signs (both sexes):
50 mg/kg: sedation, curved body position, ruffled fur
150 mg/kg: sedation, dyspnea, ataxia, curved body position, ruffled fur
500 mg/kg: sedation, ataxia, curved body position, ruffled fur
5000 mg/kg: sedation, somnolence, dyspnea, ataxia, stiff movements, latero-abdominal position ruffled fur (males)
All surviving rats had recovered within 4 observation days.

Body weight:

For all dose levels an increase of the body weight could be observed.

Gross pathology:

50 mg/kg (killed at termination):
Males: No pathological changes
Females: No pathological findings
150 mg/kg
Found dead during the study:
male: liver- discoloured, partly, black
intestines - meterorism
killed at termination:
one male: lung, dark-red
other males: no pathological findings
females: no pathological findings
500 mg/kg:
Found dead during study:
males: lung: discoloured, dar-red
liver-discoloured, partly, black
stomach/intestines - filled with test-article
females: lung: black, mottled, partly
liver-discoloured, partly, black
stomach/intestines - filled with test-article
kidneys/spleen - black mottled
Killed at termination:
one male: no pathological findings
5000 mg/kg (males only):
lung - dark-red foci
liver - discoloured, partly, black
stomach - totally perforated, abdominal cavity totally filled with contents;
intestines - filled with reddened fluid and test article
kidneys - discoloured, partly black
spleen - discoloured, partly, black

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information according to GHS Criteria used for interpretation of results: EU

Conclusions:

The resulting LD50 value from this study for sodium sulfide 60 % is as follows: LD50 calculated = 253.8 mg for males and females.
According to the criteria specified by Directive 67/548/EC and subsequent regulations the test item is harmful if swallowed (Xn, R22) and requires classification. According to the criteria specified by Regulation (EC) No 1272/2008 and subsequent regulations the test item is toxic if swallowed (toxic category III according to GHS) and requires classification. The calculated LD50 value of 246 mg/kg bw for the most concentrated commercial form Na2S, 62 %, would lead to the same classifications.

Executive summary:

The results indicate that the LD50 calculated for the most concentrated commercial form Na₂S, 62 %, would be 246 mg/kg bw.