Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted in 2001
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Landesinstitut für Arbeitsschutz und Produktsicherheit, München, Germany
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Wistar Crl: WI(Han)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 8 - 10 weeks
- Weight at study initiation: 154 - 167 g
- Fasting period before study: Food was withheld for 16 to 19 h before until 4 h after dosing.
- Housing: The animals were housed in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding.
- Diet: Altromin 1324 maintenance diet for rats and mice, ad libitum
- Water: tap water, sulphur acidified to a pH value of approximately 2.8, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
- Step 1
From: 27 Jul 2012
To: 10 Aug 2012
- Step 2
From: 16 Aug 2012
To: 30 Aug 2012

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Justification for choice of vehicle: The vehicle was chosen due to its non-toxic characteristics.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 females (3/step)
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made several times on the day of dosing (especially during the first 30 min until 4 h after application) and once daily thereafter until the end of the study period. Animals were weighed on Days 1, 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: cut-off value
Mortality:
All animals survived until the end of the observation period.
Clinical signs:
After application of the test substance, slightly reduced spontaneous activity and slight piloerection were noticed in all animals. The effects were reversible within 4 h. Moreover, the first set of animals showed bradykinesia, kyphosis and half eyelid-closure, that reversed within 3 h after application.
Body weight:
No effects on body weight and body weight gain were observed (Table 1).
Gross pathology:
Necropsy revealed no substance-related findings.

Any other information on results incl. tables

Table 1: Absolute Body Weights and Body Weight Gain

Animals

Body weight (g)

Increase (%)

Step

Number

Day 1

Day 8

Day 15

Day 1 - 15

1

1

156

187

198

27

2

154

176

185

20

3

165

175

200

21

2

4

164

191

208

27

5

167

189

202

23

6

164

185

197

20

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