Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 Mar - 07 Apr 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study; all 5 animals were dosed at the same time.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
adopted in Dec 2001
Deviations:
yes
Remarks:
all 5 animals were dosed at the same time
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): [trade name given]
- Physical state: white crystalline powder
- Analytical purity: no data
- Lot/batch No.: 10SC8156928-2-2

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc.
- Age at study initiation: 7 weeks
- Weight at study initiation: 178 - 191 g (range)
- Fasting period before study: from approximately 20 h before dosing until 4 h after dosing
- Housing: animals were housed in groups of 2-3 in suspended aluminium cages with an automatic water supply system
- Diet: CRF-1 pellet diet (Oriental Yeast Co., Ltd.), ad libitum
- Water: filtered tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24± 2
- Humidity (%): 40 - 70
- Air changes (per hr): more than 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled water for injection purposes
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
10 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed for morbidity and mortality, and for clinical signs 10 and 30 min., 1, 2 and 4 h after dosing, and daily thereafter for 14 days; the body weight was recorded prior to dosing, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
Irregular respiration was observed in 1/5 rats 30 min after dosing, and in 4/5 rats 1-4 h after administration. A decrease of spontaneous activity was also noted in 1/5 animals 30 min after dosing, increasing to 2-3/5 animals 1-4 h after administration. Muscular rigidity was noted in 2-5 rats, in an increasing number from 1 to 4 h after administration. Stains around the eyes and snout were observed in all 5 animals on Day 1, persisting until Day 2 in 1/5, while stains around the mouth was observed in 3/5 Day 1. Clonic convulsion were noted in 1/5 rats 4h after dosing. Urinary incontinence were noted in 1/5 rats during Day 1. No clinical signs were observed from Day 3 onward.
Body weight:
No effect on body weight was noted.
Gross pathology:
No substance-related findings were noted during the necropsy and macroscopic examination.

Any other information on results incl. tables

Table 1

 

Appearance of clinical signs, time after treatment

 

Hours

Days

 

0.1

0.5

1

2

4

1

2

3-14

Clinical signs

Number of animals examined

5

5

5

5

5

5

5

5

No abnormal signs

5

4

1

1

0

0

4

5

Clonic convulsions

0

0

0

0

1

0

0

0

Muscular rigidity

0

0

2

3

5

0

0

0

Urinary incontinence

0

0

0

0

0

1

0

0

Irregular respiration

0

1

4

4

4

0

0

0

Decrease of spontaneous activity

0

1

3

2

3

0

0

0

Stains (around eyes)

0

0

0

0

0

5

0

0

Stains (around snout)

0

0

0

0

0

5

1

0

Stains (around mouth)

0

0

0

0

0

3

0

0

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified