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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:
end on 21-SEP-2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Uronium hydrogen sulphate
EC Number:
244-343-6
EC Name:
Uronium hydrogen sulphate
Cas Number:
21351-39-3
IUPAC Name:
amino(hydroxy)methaniminium hydrogen sulfate
Details on test material:
- Name of test material (as cited in study report): aduct urea-sulfuric
- Physical state: liquid
- Stability under test conditions: stable at room temperature & normal use to 30°C
- Storage condition of test material: dry, ventilated well, away from inflammable materials

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sulzfeld
- Age at study initiation: no data
- Weight at study initiation: between 153g and 171g
- Fasting period before study: yes
- Housing: transparent macrolone cages (floor area 810 cm²) with three animals in each cage.
- Diet: free access to pelleted diet "Altromin 1324"
- Water: free access to bottles with domestic quality drinking water, which was acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3°C
- Humidity: at least 30% and preferably not exceed 70%
- Air changes: 10 times/hour
- Photoperiod: 12hrs dark / 12hrs light

IN-LIFE DATES: from 6 July 2010 to 1 September 2010

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle: 10 ml/kg bw
- Justification for choice of vehicle: no data

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

DOSAGE PREPARATION: no data

CLASS METHOD
- Rationale for the selection of the starting dose: litterature value
No. of animals per sex per dose:
300 and 2000 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> each rat was observed 30 minutes, 2 hrs, 4 hrs and 6 hrs after the administration and thereafter daily
> the body weight was determined on days 0, 7 and 14
- Necropsy of survivors performed: yes
Statistics:
not applicable

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All six animals survived at a dose of 300 mg/kg bw. One rat per group died after the administration of the test item in a dose of 2000 mg/kg bw.
Clinical signs:
300 mg/kg bw: huntched posture and piloerection on the day of application after 30 minutes; 2 hrs and 4 hrs. After 6 hrs the rats still showed piloerection. From day 1 to the end of the observation period on day 14 all animals were free of any abnormalities.
2000 mg/kg bw: signs of toxicosis ranging from slight to severe were observed. On the day of application, piloerection, huntched posture. Two animals were found dead on day 1 and on day 3. From day 4 to the end of the observation period on day 14 surviving animals were free of any abnormalities.
Body weight:
The development of the body weight was normal in surviving animals.
Gross pathology:
There were no pathological signs detected in the necropsy with the exception of the following findings:
- the rat no. 7 had died in the night from day 2 to day 3 and it was clearly discernible that the other animals in the cage had eaten from the body already. Feeding traces were seen on the heart, lungs, abdomen and liver. The gastrointestinal tract was filled.
- In the rat no. 12 (2000 mg/kg bw, died on day 1) bloody stomach contents, slightly edematous intestinal wall and bluish extremities were noted.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Oral LD50 > 2000 mg/kg bw
Executive summary:

In an acute oral toxicity study (OECD 423, GLP), groups of fasted Wistar rats (2x3 female/dose) were given a single oral dose of uronium hydrogen sulphate in water at doses of 300 and 2000 mg/kg bw and observed for 14 days.

 

Oral LD50 Females > 2000 mg/kg bw

All six animals survived at a dose of 300 mg/kg bw. One rat per group died after the administration of the test item in a dose of 2000 mg/kg bw.

Huntched posture and piloerection were observed on the day of application in each group.

The development of the body weight was normal in surviving animals.

There were no pathological signs detected in the necropsy in the surviving animals. In animals dead during the study, the following findings were observed:

-         the other animals in the cage had eaten from the body of the dead animal;

-         bloody stomach contents, slightly edematous intestinal wall and bluish extremities in the other rat.

 

Uronium hydrogen sulphate is of low toxicity based on the LD50 in females. The test item is not classified for acute oral toxicity according to EU criteria (DSD and CLP).