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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
Study period:
1994-12-02 to 1994-12-16
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 stability of the test item was not stated. - According to the guideline, the volume should not exceed 1 ml/100g body weight , except in the cases of aqueous solutions where 2 ml/100g may used. In this study a volume of 3.40 ml/kg was administered to the rats.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
, adopted 1987-02-24
Deviations:
yes
Remarks:
, see "Rationale for reliability"
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Potassium thiosulfate
- Molecular formula: K2S2O3
- Physical state: Clear light yellow liquid
- Active ingredient: 49.33 % K2S2O3
- Lot No.: 11-074-PHX
- Storage condition of test material: Room temperature
- Density: 1.47 g/ml
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 Laboratories, Inc., Portage, Michigan
- Weight at study initiation: mean weight males: 254 g (prefasted) and 224 g (fasted); mean weight females: 233 g (prefasted) and 212 g (fasted)
- Fasting period before study: Fasted overnight prior to test substance administration. Animals were returned to ad libitum feeding afer dosing.
- Housing: The animals were housed individually in suspended stainless steel cages. All housing and care were based on the standards recommended by the Guide for the Care and Use of Laboratory Animals.
- Diet: Purina Certified Rodent Chow #5002 was provided ad libitum except during fasting.
- Water (ad libitum): Municipal tap water treated by reverse osmosis
- Quarantine period: Minimum of five days

ENVIRONMENTAL CONDITIONS
- Temperature: 18.9 - 21.7 °C
- Relative humidity: 42 - 62 %
- Air changes: Ten to twelve air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: Individual doses were calculated based on the animal's fasted (day 0) body weight.
- Dose volume: 3.40 ml/kg
- Concentration: 100 %

DOSAGE PREPARATION: The test article was administered as received by the Sponsor.
No further information on the oral exposure was stated.
Doses:
5000 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: Limit test animals were observed for clinical abnormalities two times on the study day 0 (postdose) and daily thereafter (days 1-14). A mortality check was performed twice daily, in the morning and afternoon. individual body weights were obtained for the limit test animals prior to fasting (day-1), prior to dosing on day 0 and for all surviving animlas on days 7 and 14.
- Necropsy of survivors performed: Yes
All limit test animals which died spontaneously during the study or were euthanized (carbon dioxide inhalation) at study termination (day 14) were necropsied. Body cavities (cranial, thoracic abdominal and pelvic) were opened and examined. No tissues were retained.
No further information on the study design was stated.
Statistics:
Data from the limit test were analyzed and an LD50 value estimated as follows:
< 50 % Mortality: LD50 was estimated as greater than the administered dose
= 50 % Mortality: LD50 was estimated as equal to the administered dose
> 50 % Mortality: LD50 was estimated as less than the administered dose.
Body weight means and standard deviations were calculated separately for males and females.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: The stated LD50 is based on the aqueous solution. The LD50 of the pure test substance was greater than 2500 mg/kg (was calculated from 49 % solution).
Mortality:
All mortality occurred by study day 1. One female died by study day 1. All the other animals survived.
Clinical signs:
Clinical abnormalities observed during the study included transient incidences of urine stains.
MALES:
In one male soft tools (study day 1) and fecal stain (study day 1) were observed.
FEMALES:
In one females hair loss on the left shoulder (study days 4 - 14), hairloss on the left hindlimb (Study days 6 - 14), hairloss on the left hip (study days 8 - 14), hairloss on the abdominal region (study days 9-14 and hairloss on the left forelimb (study days 13-14) were observed.
In an other female few feces (study day 1) and urine stains (study day 1) were observed.
In a third female urine stains (study day 1) were observed.
Body weight:
Body weight gain was noted for all animals during the test period.
Gross pathology:
For the animal that died, internal gross findings included reddened thyroid, mottled lungs, blackish-purple liver, dark red foci and reddened mucosa in the stomach, abnormal coloured fluid/mucoid contents in the digestive tract and congested meningeal vessels of the brain. No gross internal findings were observed at necropsy on the study day 14.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this test, the acute oral LD50 of potassium thiosulfate solution was estimated to be greater than 5000 mg/kg (for pure test item > 2500 mg/kg) in the rat.
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.