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: Comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
Standard assessment of acute oral toxicity
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test substance (as cited in study report): 1, 8 - Diazabicyclo (5, 4, 0) undecen-7
- Analytical purity: 99,6% (data from study report no. 10F0064/905074)
- Physical state: liquid
- Substance number: 90/64

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. Thomae GmbH, Biberach, Germany
- Mean weight at study initiation: 190 g (males); 179 g (females); (+/- 20% of mean weight)
- Fasting period before study: 16 h (food only)
- Housing: 5/cage, stainless steel wire mesh cages, type DK-III (Becker & Co., Castrop-Rauxel, Germany)
- Diet: Kliba-Labordiaet 343, Klingenthalmuehle AG, Kaiseraugust, Switzerland; ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2.15, 6.81 and 20.0 g/mL
- Justification for vehicle: aqueous formulation corresponds to the physiological medium

MAXIMUM DOSE VOLUME APPLIED: 10.0 mL/kg bw
Doses:
215, 681 and 2,000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: several times on the day of adinistration; at least once each work day
- Frequency of weighing: day 0, 7 and 13
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 215 - < 681 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 0/10 animals died in the 215 mg/kg bw dose group and 9/10 animals died in the 681 mg/kg bw dose group within 1 day.
Mortality:
- 215 mg/kg bw: 0/10 animals died
- 681 mg/kg bw: 9/10 animals died (3 males and 4 females died within 1 hour after application, 1 further male and 1 further female died within 1 day)
- 2000 mg/kg bw: 10/10 animals died (2 males and 5 females died within 1 hour after application, 3 further males died within 1 day)
Clinical signs:
- 215 mg/kg bw: no clinical signs were observed
- 681 and 2000 mg/kg bw: poor general state, dyspnoea, apathy, abdominal position, staggering, tremor, twitching, cyanosis, exophthalmos, atonia, paresis (for details see table below)
Body weight:
All surviving animals gained weight during the observation period.
Gross pathology:
- Animals that died: general congestion in some animals; stomach: diapedetic hemorrhages
- Sacrificed animals: No pathologic findings were noted.

Any other information on results incl. tables

Clinical signs (males):

Dose (mg/kg bw)

215

681

2000

Poor general state

 

0 h – 5 h

0 h – 1 h

Dyspnoea

 

 

0 h – 1 h

Apathy

 

0 h – 5 h

0 h – 1 h

Abdominal position

 

 

1h

Staggering

 

0 h – 1 h

0 h – 1 h

Tremor

 

 

1h

Twitching

 

0 h – 1 h

1h

Cyanosis

 

 

1h

Exophthalmos

 

 

1h

 

 Clinical signs (females):

Dose (mg/kg bw)

215

681

2000

Poor general state

 

0 h – 1 h

0 h

Dyspnoea

 

0 h – 1 h

0 h

Apathy

 

0 h – 1 h

0 h

Abdominal position

 

 

0 h

Staggering

 

0 h – 1 h

0 h

Atonia

 

 

0 h

Paresis

 

 

0 h

Twitching

 

0 h – 1 h

 

 

 

Mean body weight (males):

Dose (mg/kg bw)

215

681

2000

Day 0

197 g

190 g

182 g

Day 7

269 g

252 g

 

Day 13

302 g

285 g

 

 

Mean body weight (females):

Dose (mg/kg bw)

215

681

2000

Day 0

180 g

179 g

179 g

Day 7

213 g

 

 

Day 13

223 g

 

 

 

 

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of DBU in the rat was found to be 215 -681 mg/kg bw under the conditions of this study.
Executive summary:

Groups of Wistar rats (5/sex) were gavaged with DBU (in water) at dose levels of 215, 681 or 2000 mg/kg bw and observed for 14 days. Deaths occurred at 2000 mg/kg bw (10/10) and at 681 mg/kg bw (9/10). Signs of toxicity (reduced general state, dyspnoea, apathy, abdominal position, staggering, tremor, twitching, cyanosis, exophthalmos, atonia, paresis) were also observed at these dose levels. No effects of treatment were observed at 215 mg/kg bw. The acute oral LD50 of DBU in the rat was therefore found to be 215 -681 mg/kg bw under the conditions of this study.