Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 March 2009 and 02 April 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Recently conducted GLP compliant study using the most recent test methods

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
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): JKY-214
- Physical state: white solid
- Analytical purity: No information
- Lot/batch No.: Y002E
- Expiration date of the lot/batch: No information
- Stability under test conditions: No information. Assumed stable due to no data to the contrary
- Storage condition of test material: room temperature in the dark
- Other:

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 166-182 g
- Fasting period before study: overnight prior to dosing and 3-4 hours post dosing
- Housing: Group housing up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): free access to rodent diet
- Water (e.g. ad libitum): free access to mains water
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25oC
- Humidity (%): 30-70%
- Air changes (per hr): at least 15 changes / hr
- Photoperiod (hrs dark / hrs light): 12 hrs light/ 12 hrs dark


IN-LIFE DATES: 14 days, dates not specified

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
peanut oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 300 mg/kg (preliminary); 2000mg/kg (main study)
- Amount of vehicle (if gavage): not reported
- Justification for choice of vehicle: Substance not soluble in water
- Lot/batch no. (if required): not reported


MAXIMUM DOSE VOLUME APPLIED: 2000mg/kg


DOSAGE PREPARATION (if unusual): suspension in vehicle


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: N/A
Doses:
300mg/kg preliminary
2000mg/kg main study
No. of animals per sex per dose:
300mg/kg: 1 female
2000mg/kg: 5 females

Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations were made V2, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily.
Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Not performed

Results and discussion

Preliminary study:
5.1 Dose Level - 300 mg/kg
Individual clinical observations and mortality data are given in table
Dose Level mg/kg Animal Number and Sex Effects Noted After Dosing (Hours)
Effects Noted During Period After Dosing
(Days)
1/2 1 2 4 1 2 3 4 5 6 7 8 9 10 11 12 13 14
300 1-0 Female 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There was no mortality.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
The animal showed expected gains in bodyweight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy
Other findings:
none

Any other information on results incl. tables

Individual Clinical Observations and Mortality Data - 2000 mg/kg


Dose Level mg/kg

Animal Number and Sex

Effects Noted After Dosing (Hours)

Effects Noted During Period After Dosing (Days)

1/2

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

2-0 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-0 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-1 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-2 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-3 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Individual Bodyweights and Bodyweight Changes - 2000 mg/kg

Dose Level mg/kg

Animal Number and Sex

Bodyweight (g) at Day

Bodyweight Gain (g) During Week

0

7

14

1

2

2000

2-0 Female

176

206

215

30

9

3-0 Female

166

167

181

1

14

3-1 Female

178

192

201

14

9

3-2 Female

174

200

212

26

12

3-3 Female

182

197

205

15

8

Individual Necropsy Findings - 2000 mg/kg


Dose Level mg/kg

Animal Number and Sex

Time of Death

Macroscopic Observations

 

2-0 Female

Killed Day 14

No abnormalities detected

 

3-0 Female

Killed Day 14

No abnormalities detected

2000

3-1 Female

Killed Day 14

No abnormalities detected

 

3-2 Female

Killed Day 14

No abnormalities detected

 

3-3 Female

Killed Day 14

No abnormalities detected

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance is not acutely toxic by oral exposure
Executive summary:

The acute oral toxicity has been assessed by means of fixed dose procedure according to EU method B1bis in compliance with GLP. As no mortality or clinical signs were observed at the highest test concentration required by the test guideline and bodyweight gain was as expected for all aninmals the substance is considered not acute toxic by oral administration.