Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 - 26 Feb 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
17 December 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
Commission Directive 2004/73/EC
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM, UK GLP Monitoring Authority
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Remarks:
HsdRccHan®™:WIST®™
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 158 - 186 g
- Fasting period: overnight immediately before dosing and approx. 3 - 4 h after dosing
- Housing: groups of up to 4 animals in suspended solid-floor polypropylene cages furnished with woodflakes
- Water: free access to mains drinking water
- Diet: free access to food (2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK)
- Acclimation period: at least 5 days

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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.
- Concentration in vehicle: 100 mg/mL

MAXIMUM DOSE VOLUME APPLIED:
- Dose volume: 10 mL/kg bw

DOSAGE PREPARATION:
The test material was prepared at a concentration of 100 mg/mL. Due to the nature of the test material it was not possible to formulate at a 200 mg/mL concentration. To achieve the dose level of 2000 mg/kg bw, two separate amounts of 1000 mg/kg bw were administered at a 1 h interval.

- Rationale for the selection of the starting dose: Using available information on the toxicity of the test material, 2000 mg/kg bw was chosen as the starting dose.
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: Clinical observations were made 0.5, 1, 2, and 4 h after dosing, subsequently once daily until the end of the observation period. Morbidity and mortality checks were made twice daily. Individual body weights were recorded on the day of dosing (Day 0) and on Days 7 and 14 post-administration.
- Necropsy of survivors performed: yes, gross necropsy (external examination and opening of the abdominal and thoracic cavities, appearance of any macroscopic abnormalities was recorded)
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths. All (5/5 females) animals survived the limit dose of 2000 mg/kg bw.
Clinical signs:
There were no signs of systemic toxicity. Black stained faeces were observed one to five days after dosing.
Body weight:
All animals showed expected gains in bodyweight.
Gross pathology:
No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1: Individual Clinical Observations and Mortality Data

Dose level [mg/kg bw]

Animal no. and sex

Effects noted after dosing [h]

Effects noted during period after dosing [days]

0.5

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000*

1-0

Female

0

0

0

0

0F

0F

0F

0F

0F

0

0

0

0

0

0

0

0

0

2-0

Female

0

0

0

0

0F

0F

0F

0F

0

0

0

0

0

0

0

0

0

0

2-1

Female

0

0

0

0

0F

0F

0F

0F

0

0

0

0

0

0

0

0

0

0

2-2

Female

0

0

0

0

0F

0F

0F

0F

0

0

0

0

0

0

0

0

0

0

2-3

Female

0

0

0

0

0F

0F

0F

0F

0

0

0

0

0

0

0

0

0

0

*: Due to the nature of the test material it was not possible to formulate at a 200 mg/mL concentration. To achieve the dose level of 2000 mg/kg bw, two separate amounts of 1000 mg/kg bw were administered at a 1 h interval.

0: no signs of systemic toxicity

F: black stained faeces

 

Table 2: Individual Bodyweights and Bodyweight Changes

Dose level [mg/kg bw]

Animal no. and sex

Bodyweight [g] at Day

Bodyweight gain [g] during Week

0

7

14

1

2

2000*

1-0 Female

158

170

183

12

13

2-0 Female

181

195

199

14

4

2-1 Female

186

191

209

5

18

2-2 Female

178

186

192

8

6

2-3 Female

163

174

180

11

6

*: Due to the nature of the test material it was not possible to formulate at a 200 mg/mL concentration. To achieve the dose level of 2000 mg/kg bw, two separate amounts of 1000 mg/kg bw were administered at a 1 h interval.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
The acute oral LD50 of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bw.