Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Strain: Hsd Cpb:WU (SPF)
- Age at study initiation: 8-9 weeks
- Mean weight at study initiation: 210-217 g (males) or 154-162 g (females)
- Housing: in groups of 3 animals
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 5
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: formulated in demineralized water with the aid of Cremophor EL 2% (v/v)
Details on oral exposure:
- Application volume: 10 mL/kg bw

- Rationale for the selection of the starting dose:
As described in the flow charts of Annex 2, OECD guideline 423, the starting dose level should be that which is most likely to produce mortality in
some of the dosed animals. Therefore, the limit dose 2000 mg/kg bw was chosen as starting dose.
Doses:
2000 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at least once daily (clinical signs, mortality) or once weekly (weight gain)
- Necropsy of survivors performed: yes
Statistics:
none (limit test)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
other: LD50 cut-off
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Mortality:
One female died on day 2 after administration of 2000 mg/kg bw. The other 5 animals survived the treatment.
Clinical signs:
At 2000 mg/kg bw in males and females the motility and reactivity were decreased, the animals showed narrowed palpebral fissures, and the breathing was labored. Additionally, in females piloerection and a uncoordinated gait were observed. The signs observed started 40 minutes after administration and lasted up to day 5 of the study.
Body weight:
Body weight development was not affected.
Gross pathology:
No gross pathological findings were observed at the end of the post-treatment observation period. In the female animal that died during the observation period a pale discoloration of kidneys was detected.
Other findings:
none

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Executive summary:

The acute oral toxicity of Bay 38-7268 was low with a LD50 exceeding 2500 mg/kg bw in rats (cut-off value) according to OECD TG 423. At the limit-dose 2000 mg/kg one female animal died and in both genders clinical signs were observed up to day 5 after administration. The main clinical findings were decreased motility, decreased reactivity, uncoordinated gait, narrowed palpebral fissures, piloerection and labored breathing.

Administration was tolerated without effects on body weight gain and gross pathological findings.