Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
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 without an effect on the results: - The purity and stability are missing. -According to the guideline, the observation period should be at least 14 days. In this study the animals were only observed for 7 days. This was not regarded to influence the results, since no animals died after 24 hours. - According to the guideline, the animals should be acclimatised to the laboratory condition for at least 5 days. This information was missing from the report. - According to the guideline, the volume administered to the animals should not exceed 2ml/100 g. In this report the volume administered was not stated. - The housing and environmental conditions were not stated, which according to the guideline should be included. - According to the guideline, animals should be fasted prior to administration of the test material. It was not stated in the report if the animals were deprived of food before test item administration. - According to the guideline the animals should be observed at least once a day and the body weight determined before administration, weekly thereafter and at death. The animals were not observed daily and the body weight was only determined before administration.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report Date:
1974

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
, see "rationale for reliablity"
GLP compliance:
no
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): Dipotassium disulphite (K2S2O5)
- Physical state: Solid
- Other: Sales product in wine production and preserving agent
No further information on the test material was stated.

Test animals

Species:
rat
Strain:
other: Gassner
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: mean 170 g (male), 166.0 g (female)
No further information on the test animals was stated.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2%, 16%, 20%, 25%, 30%

DOSAGE PREPARATION (if unusual): 90 min prior to dosing
No further information on the oral exposure was stated.
Doses:
200, 1600, 2000, 2250, 2500, 3200, 6400 mg/kg bw (2 %, 16 %, 20 % 25 %, 25 %, 30 % and 30 % respectively)
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: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs, body weight (determined before the study started), and gross pathology
No further information on the study design was stated.
Statistics:
not stated

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: The LD50 was determined after an observation period of 7 days.
Mortality:
6400 mg/kg bw: 5/5 males within 1 h; 5/5 females within 1 hour
3200 mg/kg bw: 1/5 male within 1 h, 4/5 males within 24 h; 3/5 females within 1 h, 5/5 females within 24 h
2500 mg/kg bw: 2/5 males within 24 h; 3/5 females within 1 h, 5/5 females within 24 h
2250 mg/kg bw: 0/5 males; 3/5 females within 24 h
200 - 2000 mg/kg bw: 0/5 males; 0/5 females
Overall, when animals died they died within 24 hours.
Clinical signs:
The following clinical signs were observed immediately after the beginning of the study up to 20 minutes thereafter:
6400 mg/kg bw: staggering, abdominal position, accelerated respiration,convulsions (Animals died within 15 minutes)
3200 mg/kg bw: staggering, abdominal position, accelerated respiration (On the following days the suriving animals were without symptoms)

Further was observed during the observation period:
2500 mg/kg bw: Immediately after the start of the study no symptoms were observed. After 20 minutes the following clinical signs were observed in females: staggering, abdominal position, accelerated respiration. After 3 hours accelerated respiration was to some extent observed in males. (On the following days the suriving animals were without symptoms)

2250 mg/kg bw: The animals showed no clinical signs in the beginning. After approx. 3 h accelerated respiration was seen in the females and later slight apathy. The next morning all surviving animals were without symptoms.


200 - 2000 mg/kg bw: No clinical symptoms were observed.
Body weight:
Not stated
Gross pathology:
6400 mg/kg: Heart: acute cardiac dilation; stomach: filled with thin fluid content, ecchymosis, duodenum is diffused reddened
3200 mg/kg: Heart: acute cardiac dilation, venous congestical hyperemia ; stomach: filled with thin fluid content, ecchymosis, duodenum is diffused reddened; Intestine: light diarrhoeic content; liver: relatively dark; kidneys: lighten kidneys
2500 mg/kg: Heart: acute cardiac dilation, venous congestical hyperemia; stomach: filled with thin fluid content, light diffused reddening, some animals had a bloody mucosa with bloody content; Intestine: moderate diarrhoeic content
2250 mg/kg: Heart: acute cardiac dilation, venous congestical hyperemia; stomach: extented, fluid content, diffused reddened, vessels heavy injected; intestine: slight diarrhoeic content; kidney: bloody imbibition
2000 mg/kg: No gross pathology found
1600 mg/kg: No gross pathology found
200 mg/kg: No gross pathology found
Other findings:
not stated

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A LD50 >2000 mg/kg bw was found determined for male and female rats after an observation time of 7 days.
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.