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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Comparable to guideline study reliable with restrictions Minor deviations with no effect on the results: - The purity and stability were missing. - The number of animals showing signs of toxicity was missing. -The method for LD50 calculation was not stated.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
, see "Rationale for reliability"
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): sodium sulphite water-free Z
No further information on the test material was stated.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld
- Age at study initiation: ca. 12 weeks
- Weight at study initiation: mean weight males : 210 g (Individual weights of males: 230 g, 180 g, and 220 g); mean weights females: 190 g ( individual weights of females: 180 g, 180 g, and 210 g)
- Fasting period before study: The animals were given no food for 16 hours before administration, but water was available ad libitum.
- Housing: Animals were housed in groups of 5. They were housed in V-II-A- stainless steel wire mesh cages, Type DK-III (supplied by Becker & Co., Castrop-Rauxel); Animals of comparable weights (+/- 10 g) in one cage.
- Diet: ssniff R; Firma ssniff, Versuchstierdiaeten; 4470 Soest
- Water (ad libitum): Fully demineralized water each workday; tap water on public holidays
- Acclimation period: Acclimatization in the animal care unit for at least one week.

ENVIRONMENTAL CONDITIONS
- Temperature: 20-26°C
- Relative humidity: 45-75 %
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was not stated.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 31.6 % (Dosis: 3160 mg/kg), 26.1 % (Dosis: 2610), and 21.5 % (Dosis: 2150 mg/kg)
- Justification for choice of vehicle:: Aqueous preparation corresponding to the physiological medium.

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg
No further information on the oral exposure was stated.
Doses:
2150, 2610, 3160 mg/kg
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Groups were weighed before administration, and on days 3, 7, and 13 after application. Recording of signs and symptoms <15 min, 15 min, 30 min, 1 h, 2 h, 4 h and 5 h after test substance administration and then once each workday. Check for moribund and dead animals twice each workday and once daily on public holidays.
- Necropsy of survivors performed: yes
- Pathology: Withdrawal of food 16 hours before sacrifice with CO2; then necropsy with gross-pathological examination. All animals that die are necropsied as early as possible.
No further information on the study design was stated.
Statistics:
No data

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 610 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 150 - < 2 610 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 5 % level of significance
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 2 746 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Value obtain through interpolation.
Mortality:
Please refer to table below ("Any other infromation on results incl. tables")
Clinical signs:
The following symptoms were observed:
MALES
3160 mg/kg:
- Dyspnoea: 15 minutes - 3 days
- Apathy: 30 minutes - 3 days
- Abnormal position: 4 hours
- Staggering: 30 minutes - 3 days
- Tremor: 4 hours - 3 days
- Tremble: 4 hours - 3 days
- Jumping convulsions: 4 hours
- Opisthotonus: 4 hours
- Clonic convulsions: 4 hours
- Ruffled fur: 2 hours - 3 days
- Diarrhea: 4 hours - 5 hours
- Cyanosis: 4 hours - 5 hours
- Exsiccosis: 4 hours - 3 days
- Salivation: 4 hours - 5 hours
- Cachexia: 3 days
- Poor general state: 30 minutes - 3 days

2610 mg/kg:
- Dyspnoea: 1 hour - 1 day
- Apathy: 1 hour - 1 day
- Staggering: 1 hour - 1 day
- Ruffled fur: 2 hours - 1 day
- Poor general state: 1 hour - 1 day

2150 mg/kg:
- Dyspnoea: 1 hour - 5 hours
- Apathy: 1 hour - 5 hours
- Staggering: 1 hour - 5 hours
- Ruffled fur: 1 day
- Poor general state: 1 hour - 5 hours

FEMALES:
3160 mg/kg
- Dyspnoea: 15 minutes - 4 hours
- Apathy: 15 minutes - 4 hours
- Abnormal position: 2 hours - 4 hours
- Staggering: 15 minutes - 4 hours
- Atony: 4 hours
- Tremble: 4 hours - 3 days
- Ruffled fur: 2 hours - 4 hours
- Diarrhea: 4 hours
- Cyanosis: 4 hours
- Exsiccosis: 4 hours
- Salivation: 4 hours
- Ptosis: 2 hours - 4 hours
- Poor general state: 15 minutes - 4 hours

2610 mg/kg:
- Dyspnoea: 1 hour - 2 hours
- Apathy: 1 hour - 2 hours
- Staggering: 1 hour - 2 hours
- Biting convulsions: 2 hours
- Ruffled fur: 2 hours
- Poor general state: 1 hour - 2 hours

2150 mg/kg:
- Dyspnoea: 15 minutes - 5 hours
- Apathy: 15 minutes - 5 hours
- Staggering: 15 minutes - 5 hours
- Tremble: 4 hours - 5 hours
- Ruffled fur: 4 hours - 2 days
- Poor general state: 15 minutes - 5 hours
Body weight:
Please refer to table below ("Any other infromation on results incl. tables")
Gross pathology:
MALE ANIMALS:
Animal that died:
3160 mg/kg: dilated intensely reddened mucosa, filled with blood-colored liquid; small intestine: atonic, intensely reddened mucosa, blood-red liquid content.
2160 mg/kg: congestive hyperemia; stomach: in the glandular stomach reddened mucosa, filled with liquid; intestine: atonic, intensely filled with liquid.
Sacrificed animals: no findings

FEMALE ANIMALS:
Animal that died:
3160 mg/kg: dilated intensely reddened mucosa, filled with blood-colored liquid; small intestine: atonic, intensely reddened mucosa, blood-red liquidcontent.
2160 mg/kg: congestive hyperemia; stomach; in the glanduar stomach reddened mucosa, filled with liquid; intestine: atonic, intensely filled with liquid.
Sacrificed animals: no findings
Other findings:
No data

Any other information on results incl. tables

Body weights (mean weights in g):

 Male animals    Start of the study After 3 days  After 7 days  After 13 days
  3160 mg/kg  230  178    
   2610 mg/kg  180  212  248  292
   2150 mg/kg  220  260  295  321
Female animals    Start of the study  After 3 days  After 7 days  After 13 days
   3160 mg/kg  180      
   2610 mg/kg  180      
   2150 mg/kg  210  232  240  245

Mortality:

 Male animals  3160 mg/kg  2610 mg/kg  2150 mg/kg
 Dead animals after  1 hour  0/5  0/5  0/5
   1 day  4/5  1/5  0/5
   2 days  4/5  1/5  0/5
   7 days  5/5  1/5  0/5
   14 days  5/5  1/5  0/5
 Female animals    3160 mg/kg  2610 mg/kg  2150 mg/kg
 Dead animals after  1 hour  0/5  0/5  0/5
   1 days  5/5  5/5  0/5
   2 days  5/5  5/5  0/5
   7 days  5/5  5/5  0/5
   14 days  5/5  5/5  0/5

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as acute toxic via the oral route.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the oral route.