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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999

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 (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

1
Chemical structure
Reference substance name:
Perhydroimidazo[4,5-d]imidazole-2,5-dione
EC Number:
207-821-5
EC Name:
Perhydroimidazo[4,5-d]imidazole-2,5-dione
Cas Number:
496-46-8
Molecular formula:
C4H6N4O2
IUPAC Name:
perhydroimidazo[4,5-d]imidazole-2,5-dione
Specific details on test material used for the study:
Batch number: Zwischenprodukt aus Partie 692.
Date of manufacturing: 27 July 1998.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Test Animals
Source: Boehringer Ingelheim Pharma KG.
Age at Study initiation: Young Adults.
Weight at Study Initiation: 150g - 300g (+/- 20% of the mean weight).
Fasting period before Study: 16 hours.
Housing: Single Housing.
Diet: Kliba-Labordiaet, Klingentalmuehle AG Kaiseraugst, Switzerland, ad libitum.
Water: Tap water ad libitum per day.
Acclimatisation Period: at least 1 week.

Environmental Conditions
Temperature (°C): 20 - 24.
Humidity (%): 30-70.
Air changes (per hour): Not Reported.
Photoperiod (hrs dark/hrs light): 12/12.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Tylose CB
Details on oral exposure:
Time of day of administration: Morning.
Observation Period: 14 days.
Date of first administration: 07 October 1998.
Date of last administration: 13 October 1998.
Doses:
Administered dose: 2000 mg/kg.
Concentration: 20g/100mL.
Administration volume: 10mL/kg.
No. of animals per sex per dose:
3.
Control animals:
no
Details on study design:
Route of administration: Single oral administration by gavage.
Fasting peroiod: No feed at least 16 hours before administration of test item, but water was available ad libitum.
No. of animals per dose: 3 male animals and/or 3 female animals.
Form of administration: Suspension.
Test substance formulation with: 0.5% Tylose CB 30.000 (cleaned sodiumcarboxy with: methylcellulose from Hoechst AG) in aqua bidest.
Reason for vehicle: Aqueous formulation corresponds to the physiological medium.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
None recorded.
Clinical signs:
No abnormalities were recorded.
Body weight:
Mean Body Weights of Males (g)
Before Study: 181
After Study: 286

Mean Body Weights of Females (g)
Before Study: 176
After Study: 224
Gross pathology:
Necropsy findings of the animals sacrificed at the end of the study (all of the animals) were diffuse, dark red discoloration in all lobes of the lung.

Any other information on results incl. tables

Individual bodyweight of the male animals(g):

Dose  2000mg/kg, weight day:   0           7        13

cage

205

180

261

302

cage

206

184

259

287

cage

207

179

250

269

 

Individual body weight of the female animals (g):

 

Dose  2000mg/kg, weight day

0

7

13

 

cage 190

178

213

229

 

cage 191

176

206

215

 

cage 192

174

212

227

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
As no mortalities occurred at any concentration, the LD50 is concluded to be >2000mg/kg of bw.
Executive summary:

The study was performed according to OECD 423, EC method B1 tris Acute Toxicity (Oral), and according to GLP provisions. It aimed to assess the acute oral toxicity of glycoluril following a single oral administration in the Wistar strain rat, and the time course of response. It also aimed to identify any delayed or irreversible effects resulting from sub-lethal doses. A group of three fasted female rats were treated with the test material at a dose level of 2000 mg/kg bodyweight. Because no mortality occurred, this was followed by a group of three fasted male rats at the same dose level. The test material was administered orally as a suspension in 0.5% Tylose CB 30.000 in aqua bidest. All of the animals showed expected gains in bodyweight over the course of the study. Necropsy findings of the animals sacrificed at the end of the study (all of the animals) were diffuse, dark red discoloration in all lobes of the lung. No mortalities occurred. The median lethal dose of the test material in male and female Wistar strain rats, after oral application, was found to be greater than 2000 mg/kg bodyweight.

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