Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 - 19 July 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted Dec 2001
Deviations:
no
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL- Storage condition of test material: The test substance should be stored refrigerated and protected from light- Stability: Possibility of polymerization by heat or light

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Charles River Laboratories Japan, Inc., Japan- Age at study initiation: 8.5 weeks- Weight at study initiation: Group 1 (300 mg/kg bw): 198.7 - 206.6 g; Group 2 (300 mg/kg bw): 205.4 - 214.2 g; Group 3 (2000 mg/kg bw): 208.7 - 219.2 g- Fasting period before study: Animals were fasted from the morning on the day before the administration of the test substance- Housing: 3 animals per group were housed in aluminium cages (W 17.5 cm x D 23 cm x H 18.0 cm) with stainless nets in the front and floor.- Diet: pelleted diet (American PMI feed Inc., USA), ad libitum- Water: drinking water (Chiba City Waterworks Bureau, Japan), ad libitum- Acclimation period: 6 days ENVIRONMENTAL CONDITIONS - Temperature (°C): 22 ± 3 - Humidity (%): 50 ± 20 - Air changes (per hr): 12 - Photoperiod (hrs dark / hrs light): 12/12IN-LIFE DATES: From: 24 Jun 2005 To: 15-19 Jul 2005

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE - Justification for choice of vehicle: since the test substance reacts with an aqueous solvent, it was not possible to use it for the preparation. As a result of an investigation of the solvent, it was found that 20% (w/v) solution could be prepared with corn oil, which was selected as the solvent in this study. - Lot/batch no.: 1L2174 MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw CLASS METHOD - Rationale for the selection of the starting dose: The starting dose of 300 mg/kg bw was used according to the OECD test guideline 423.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
6 (300 mg/kg bw) and 3 (2000 mg/kg bw)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days - Frequency of observations and weighing: animals were observed for general conditions immediately for 30 min and after 1, 3 and 6 h on Day 1 and thereafter daily during the observation period; individual body weights were determined on Day 0 (immediately before administration), 3 and 7 days after administration of the test substance and on Day 14 prior to sacrifice. - Necropsy of survivors performed: yes

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - <= 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
1 000 mg/kg bw
Based on:
test mat.
Mortality:
300 mg/kg bw: 0/6 females died2000 mg/kg bw: 2/3 females died on Day 0 and Day 1, respectively
Clinical signs:
300 mg/kg bw: a major decrease in locomotor activity was noted in 1/6 females after 1 - 6 h after treatment with the test substance, in 2/6 females 3 - 6 h after administration, in 1/6 females 3 h after administration and in 1/6 females 6 h after treatment with the test substance. Soiled fur periproctal was noted in 2/6 females 6 h after treatment with the test substance, persisting in 1/6 females until Day 1. Lose stool was observed in 3/6 females 1 - 3 h after administration and in 1/6 females immediately and 6 h after administration of the test substance. Bloody stool occured in 2/6 females 1 - 3 h after administration, in 1/6 females 6 h after administration and in 1/3 females 1 - 6 h after administration of the test substance.2000 mg/kg bw: prone position was determined in 1/3 females 6 h after administration. A major decrease in locomotor activity was observed in 3/3 females and fully disappeared in the surviving female on Day 1. Hypothermia and piloerection was observed in 2/3 females 6 h after administration. Soiled fur periproctal was noted in 3/3 females and fully disappeared in the surviving female on Day 4. Soiled fur eyes occured in 1/3 females on Day 3, soiled fur nose occured in 1/3 females 3 and 6 h after treatment and in 1/3 females on Days 1 - 3. Ptosis was observed in 1/3 females only on the day of treatment. Water diarrhoea occured in 3/3 females on the day of treatment and recurred the surviving female on Days 1 and 2. Bloody stool was determined in 3/3 females only on the day of treatment.Please refer to Table 1 under "Any other information on results incl. tables"
Body weight:
300 mg/kg bw: No effect on body weight gain was noted during the observation period.2000 mg/kg bw: In one female that was found dead on Day 1, a reduction of the body weight was observed compared to that at the beginning of the study (2.14%). In the surviving female, the body weight was reduced 3 days after administration of the test substance (9.72%); on Day 14 the body weight was comparable to that of the 300 mg/kg bw group.
Gross pathology:
300 mg/kg bw: Necropsy revealed no substance-related findings.2000 mg/kg bw: - In the 2 animals that died: red discoloration of the glandular stomach was observed, while in 1 of the 2 animals that died blood-like content was noted in the glandular stomach.- In the surviving female (1/3) splenic hypertrophy, hyperplasia of the mucosa of the forestomach, traces of hemorrhage in the serosa of the forestomach, and adhesion of the forestomach to adjacent organs (spleen, liver, peritoneum and diaphragm) was observed.

Any other information on results incl. tables

Table 1 Clinical signs

Dose (mg/kg bw) Finding 0 h 1 h 3 h 6 h D 1 D 2 D 3 D 4 - 14
300 mg/kg bw Normal 2/3 1/3 1/3 1/3 3/3 3/3 3/3 3/3
Decrease in locomotor activity 0/3 1/3 1/3 1/3 3/3 3/3 3/3 3/3
Soiled fur
Periproctal
0/3 1/3 1/3 2/3 0/3 0/3 0/3 0/3
Loose stool 1/3 2/3 2/3 1/3 0/3 0/3 0/3 0/3
Bloody stool 0/3 2/3 2/3 1/3 0/3 0/3 0/3 0/3
300 mg/kg bw Normal 3/3 2/3 0/3 0/3 1/3 3/3 3/3 3/3
Decrease in locomotor activity 0/3 0/3 3/3 2/3 1/3 0/3 0/3 0/3
Soiled fur
Periproctal
0/3 0/3 0/3 1/3 1/3 0/3 0/3 0/3
Loose stool 0/3 1/3 1/3 0/3 0/3 0/3 0/3 0/3
Diarrhea   0/3 0/3 1/3 0/3 0/3 0/3 0/3
Bloody stool 0/3 1/3 1/3 0/3 0/3 0/3 0/3 0/3
2000 mg/kg bw Normal 0/3 0/3 0/3 0/2 0/1 0/1 0/1 1/1
Prone position 0/3 0/3 0/3 1/2 0/1 0/1 0/1 0/1
Decrease in locomotor activity 1/3 2/3 3/3 2/2 0/1 0/1 0/1 0/1
Hypothermia 0/3 0/3 0/3 2/2 0/1 0/1 0/1 0/1
Piloerection 0/3 0/3 0/3 2/2 0/1 0/1 0/1 0/1
Soiled fur
Periproctal
0/3 3/3 2/3 1/2 1/1 1/1 1/1 0/1
Soiled fur (Red/Brown)
Eyes
0/3 0/3 0/3 0/2 0/1 0/1 1/1 0/1
Soiled fur (Red/Brown)
Nose
0/3 1/3 1/3 0/2 1/1 1/1 1/1 0/1
Ptosis 0/3 0/3 1/3 1/2 0/1 0/1 0/1 0/1
Watery diarrhea 3/3 0/3 1/3 0/2 1/1 1/1 0/1 0/1
Bloody stool 3/3 0/3 1/3 0/2 0/1 0/1 0/1 0/1

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
CLP: Acute Oral 4, H302