Perhydroimidazo[4,5-d]imidazole-2,5-dione

Acute Toxicity: oral

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

Test material information

1

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.