Disodium disulphite

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987-08-05 to 1987-09-04

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Stability of the test material was missing.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987-02-24

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Disodium disulphite

EC Number:

231-673-0

EC Name:

Disodium disulphite

Cas Number:

7681-57-4

Molecular formula:

Na2S2O5

IUPAC Name:

disodium disulphite

Test material form:

other: solid: microcrystalline powder

Details on test material:

- Name of test material (as cited in study report): Natriumbisulfit-Pulver (Sodium disulfite- powder)
- Chemical description: Sodium pyrosulfit
- Molecular formula: Na2S2O5
- Molecular weight: 190.12 g/mol
- Physical state: white, microcrystalline powder
- Use: Preserving agent, bleaching agent, and reducing agent
- Decomposition temperature: > 150°C
- Density: 1.48 kg/l
- pH-value in water: 4.4 - 4.9 (20%)
- Solubility: 650 g/l in water

Specific details on test material used for the study:

- Storage condition of test material: In the dark in a fume hood at 22°C

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG, Kastenfrund, SPF-Breed
- Age at study initiation: Males: ca. 7 weeks; females: ca.8 weeks
- Weight at study initiation: Males (n = 15): Mean weight: 195 g +/- 13 g (max. 215 g, min. 179 g); females (n = 15): Mean weight: 178 g +/- 5 g (max. 185 g, min. 168 g)
- Fasting period before study: Ca. 16 hours before administration and 3-4 hours after administration.
- Housing: Animals were housed in groups of five in Makroloncages (Type 4) on granulat of softwood.
- Diet (ad libitum): Rat diet Altromin 1324 (Altromin-GmbH, Lage/Lippe)
- Water (ad libitum): Tap water in plastic drinking bottles
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS - fully airconitioned rooms
- Temperature:: 22+/- 3°C
- Relative humidity: 50% +/- 20%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

deionised water

Details on oral exposure:

RANGE-FINDING STUDY:
Doses of the main study were selected based on a range-finding studies. The following doses were tested in one male and one female: 500, 1000, and 2000 mg/kg bw in deionised water (25% Concentration).
The following findings were made:
Both male and female died 120 minutes after the administration of 2000 mg/kg bw.
On the application day the animals showed reduced spontaneous activity, crouching, drawn in flanks, long-legged gait and irregular breatching. The symptoms of surviving animals were reversible from Day 1 on.
The animals, which died during the study had reddened mucous coat of the stomach as well as haematoma in the gastro-intestinal tract. The macroscopically examined animals, which were killed at the end of the study showed no changes.

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw.

DOSAGE PREPARATION: Sodium disulfite was dissolved in deionised water.
Concentrations:
8.0% (w/v) (Dose: 800 mg/kg bw.)
12.5% (w/v) (Dose: 1250 mg/kg bw.)
16.0% (w/v) (Dose: 1600 mg/kg bw.)
20.0% (w/v) (Dose: 2000 mg/kg bw.)

Doses:

Males: 1250, 1600, and 2000 mg/kg bw
Females: 800, 1250, and 1600 mg/kg bw

No. of animals per sex per dose:

Males: 5 per dose
Females: 5 per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The body weight of the animals were recorded weekly. The clinical signs and mortality were observed at least 10 and 30 minutes after administration, and 1, 2, 4 and 6 hours after administration. Afterwards the clinical signs and mortality were observed daily.
- Necropsy of survivors performed: Yes
The animals, which died during the study, were dissected and macrosopically examined. The animals, which survived until the end of the observation period, were killed with carbon dioxide. They were also dissected and macroscopically examined.
- Examinations performed: The symptoms and the mortality were recorded.

Statistics:

The LD50, the confidence interval, and the equation of the grade of the probit were calculated from the observed death rates using a probit analysis.

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

1 420 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 040 - <= 2 110

Remarks on result:

other: Confidence interval: P = 0.05

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

1 630 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 210 - <= 2 260

Remarks on result:

other: Confidence interval: P = 0.05

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 540 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 290 - <= 1 960

Remarks on result:

other: Confidence interval: P = 0.05

Mortality:

The following death rates were observed:
800 mg/kg bw.: Females: 0/5 (0%)
1250 mg/kg bw.: Males: 1/5 (20%; death after 60 minutes of administration); Females: 1/5 (20%; death after 70 minutes of administration)
1600 mg/kg bw.: Males: 2/5 (40%; death after 75 and 180 minutes of administration, respectively); Females: 4/5 (80%, death after 60 minutes of administration)
2000 mg/kg bw.: Males: 4/5 (80%; death after 70 minutes of administration)

Clinical signs:

other: The following clinical signs were observed in the males and females, respectively: reduced spontaneous activity, crouching, flanks drawn-in, ruffled fur, irregular breathing, and long-legged gait. In addition, latero-abdominal position, constricted palpeb

Gross pathology:

The macroscopically examination of the males and females, which died during the study, showed the following:
- gastro-intestinal tract filled with blood (Males in the 1250, 1600 and 2000 mg/kg bw. dose; females: 1250 and 1600 mg/kg bw. dose)
- Mucous coat of the stomach reddened (Males in the 1250 and 2000 mg/kg bw. dose; females: 1250 and 1600 mg/kg bw. dose)
- Liver dark discoloured (Males in the 1250, 1600 and 2000 mg/kg bw. dose; females: 1600 mg/kg bw. dose)
- Marked liver lobules (Females: 1600 mg/kg bw. dose
The animals, which were killed at the end of the observation period, were free of macroscopical changes.

Any other information on results incl. tables

The following clinical signs were observed.

Clinical sigs of the males:

1250 mg/kg bw.:

- Reduced spontaneous activity: One male after at least 30 minutes and four males after 1 hour of administration until Day 1 after administration.

- Long-legged gait: Four males at least 30 minutes after administration until Day 1 after administration.

- Crouching: Four males at least 30 minutes after administration until Day 1 after administration.

- Irregular breathing: Four males 1 hour after administration until Day 1 after administration.

- Ruffled fur: Two males 2 hours after administration.

1600 mg/kg bw.:

- Reduced spontaneous activity: Five males after at least 30 minutes, four males after 1 hour and three males after 2 hour of administration until Day 1 after administration.

- Long-legged gait: Two males at least 30 minutes and three males 1 hour after administration until Day 1 after administration.

- Crouching: Five males at least 30 minutes, four males 1 hour and 3 males 2 hours after administration until Day 1 after administration.

- Irregular breathing: Four males 1 hour after administration until 2 hours after administration.

- Ruffled fur: Two males 2 hours after administration.

- Flank drawn-in: 3 males after at least 30 minutes after administration until Day 1 after administration.

- Constricted palpebral fissure: 1 male after 1 hour of administration until 2 hours after administration

- Abdominal or lateral position: 1 male at 2 hours after administration

-Drowsiness: 1 male at 2 hours after administration

2000 mg/kg bw.:

- Reduced spontaneous activity: Five males after at least 30 minutes, one male after 1 hour of administration until 4 hours after administration.

- Crouching: Four males at least 30 minutes, and one male 1 hour after administration until 4 hours after administration.

- Irregular breathing: Four males at least 30 minutes, five males 1 hour, and onemale 2 hours after administration until 4 hours after administration.

- Ruffled fur: One male 4 hours after administration.

- Flank drawn-in: Four males after at least 30 minutes and one male 1 hour after administration until Day 1 after administration.

- Constricted palpebral fissure: 1 male at least 30 miuntes after administration until 1 hour after administration

- Abdominal or lateral position: Four males at 1 hour after administration

-Drowsiness: Four males at 4 hours after administration

Clinical sigs of the females:

800 mg/kg bw.:

- Reduced spontaneous activity: five females after 1 hour of administration until Day 1 after administration.

1250 mg/kg bw.:

- Reduced spontaneous activity: Five females after at least 30 minutes and four females after 1 hour of administration until Day 1 after administration.

- Crouching: Two females after at least 30 minutes and four females after 1 hour of administration until Day 1 after administration.

- Flank drawn-in: Two females after at least 30 minutes and four females after 1 hour of administration until Day 1 after administration.

- Irregular breathing: Two females after at least 30 minutes and four females after 1 hour of administration until Day 1 after administration.

- Ruffled fur: One female after 2 hours of administration until 4 hours after administration.

1600 mg/kg bw.:

- Reduced spontaneous activity: One female after at least 30 minutes of administration until Day 1 after administration.

- Long-legged gait: Five females at least 30 minutes and 1 female after 1 hour of administration until Day 1 after administration.

- Crouching: One females after at least 30 minutes of administration until Day 1 after administration.

- Flank drawn-in: One females after at least 30 minutes of administration until Day 1 after administration.

- Irregular breathing: One females after 2 hours of administration until Day 1 after administration.

- Ruffled fur: One females after 2 hours of administration until Day 1 after administration.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is classified as Category 4.