Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-11-27 - 2009-01-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 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 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with OECD 423
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Gelb LD 6259 (No 08/0646-1)
- Physical state: solid/ sun yellow
- Analytical purity: 87.6 area% (230 nm) rather 89.1 area% (400 nm) (Method: HPLC)
- Lot/batch No.: 0817 VP 01
- Stability under test conditions: the stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility
- Storage condition of test material: room temperature
- Other: the test substance was homogeneous by visual inspection.

Test animals

Species:
rat
Strain:
other: Wistar / Crl:WI (Han)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: young adult animals (female animals approx. 12 weeks)
- Weight at study initiation: animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: Makrolon cage, type III; single housing
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany)
- Water (e.g. ad libitum): tap water
- Acclimation period: acclimatization period at least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): the animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 20 – 24°C for temperature
- Humidity (%): 20 – 80% for relative humidity
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Olive oil Ph.Eur.
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 g/100 mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: good homogeneity in Olive oil Ph.Eur.

MAXIMUM DOSE VOLUME APPLIED:

DOSAGE PREPARATION (if unusual):
The test-substance preparation was produced for each test group shortly before administration by stirring with a high speed homogenizer (Ultra-Turrax) and a magnetic stirrer.
The homogeneity of the test-substance preparation during application was provided by stirring with a magnetic stirrer.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: by the request of the sponsor a starting dose of 2000 mg/kg body weight had been chosen in the first step with 3 female animals. Because no animal died at the first step, 2000 mg/kg body weight was administered to another group of 3 female animals in the second step.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 females per group (2 groups evaluated)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation. Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals; these records are maintained with the raw data. a check for any dead or moribund animal was made twice each workday and once on weekends and on public holidays.
- Necropsy of survivors performed: yes; necropsy with gross-pathology examination on the last day of the observation period after sacrifice by CO2- inhalation in a chamber with increasing concentrations over time.
- Other examinations performed: clinical signs, organ weights
Statistics:
not applicable

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: no animals died, no clinical signs
Mortality:
No mortality occurred.
Clinical signs:
No clinical findings were observed during clinical examination.
Body weight:
The mean body weights of the test groups increased normally throughout the study period (Table 1).
Gross pathology:
There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.
Other findings:
not applicable

Any other information on results incl. tables

Table 1: Body weights changes

 

Individual body weight changes

Dose (mg/kg bw):

2000

2000

Administration:

1

2

Animal No.:

532

533

534

mw

567

568

569

mw

Body weight at study day (g):

 

 

 

 

 

 

 

 

0

204

205

188

199

180

177

194

184

7

216

217

198

210

191

195

213

200

14

223

227

203

218

200

207

217

208

Applicant's summary and conclusion