Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 Nov - 20 Dec 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
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
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Oxon, UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 153 - 170 g
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Diet: 2014C Teklad Global Rodent diet (Harlan Teklad, Oxon, UK), ad libitum
- Water: mains drinking water, ad libitum
- 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
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: Arachis oil BP was considered to produce a formulation more suitable for dosing than distilled water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: For the purpose of the study, the test item was freshly prepared, as required, as a suspension in vehicle.
The test item was formulated within two hours of being applied to the test system. It was assumed that the formulation was stable for this duration.
No analysis was conducted to determine the homogeneity concentration or stability of the test item formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
300 mg/kg bw: 1
2000 mg/kg bw: 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made ½, 1, 2, and 4 hours after dosing and subsequently once 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
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.


Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
300 and 2000 mg/kg bw: There were no deaths.
Clinical signs:
300 and 2000 mg/kg bw: No signs of systemic toxicity were noted during the observation period.
Body weight:
300 and 2000 mg/kg bw: All animals showed expected gains in bodyweight over the observation period.
Gross pathology:
300 and 2000 mg/kg bw: No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1. Summary of individual bodyweights and bodyweight changes

Dose level [mg/kg bw]

Animal number and sex

Bodyweight [g] at Day

Bodyweight gain [g] during Week

0

7

14

1

2

300

1-0 female

159

178

191

19

13

2000

2-0 female*

160

200

218

40

18

3-0 female

164

182

195

18

13

3-1 female

163

183

194

20

11

3-2 female

170

189

192

19

3

3-3 female

153

177

192

24

15

 * Due to a dose volume calculation error the animal received a dose of at least 2000 mg/kg. As no signs of systemic toxicity were observed, this error was considered not to have affected the outcome of the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the female Wistar rat was estimated to be greater than 2000 mg/kg bw. Therefore, the test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008 (CLP) and is thus considered to be not acutely toxic by the oral route.

CLP: not classified