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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
Version 2001-12-17
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
Version 1998-07
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Identifier: CAS 80675-49-6
- Lot/batch No.: L-7015-20
- Yellow powder
- Storage conditions: Ambient temperature, no protection from light necessary
Specific details on test material used for the study:
- Identifier: CAS 80675-49-6
- Lot/batch No.: L-7015-20
- Analytical purity: 95%
- Yellow powder
- Storage conditions: Ambient temperature, no protection from light necessary

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Crl:(WI)BR rats from Charles River Deutschland GmbH, 97633 Sulzfeld, Germany.
- Age at study initiation: ~ 8 weeks at administration
- Weight at study initiation: 185 ± 2 g (3 animals of the first treatment step) 186 ± 6 g (3 animals of the second treatment step).
- Housing: single caging in Makrolon cages type III (39 cm x 23 cm bottom area, 18 cm height). Wire mesh lids. Sanitation of cages once a week.
- Diet: ad libitum, Ssniff R/M-H maintenance diet for rats and mice (item V1534-3 ) (Ssniff Spezialdiäten GmbH, 59494 Soest, Germany).
- Water: ad libitum, tap water from an automatic watering system.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ø 22.9 (continuous control and recording)
- Humidity (%): ø 48.3 (continuous control and recording)
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE:
- Concentration in vehicle: 100 mg/mL
- Amount of vehicle: 20 mL/kg
- Justification for choice of vehicle: The test substance was suspendable with water. According to the guidelines, water shall be used preferably.

MAXIMUM DOSE VOLUME APPLIED:
- 20 mL/kg

DOSAGE PREPARATION:
- The suspensions were prepared freshly before administration and were administered within 10 minutes after the preparation.

CLASS METHOD:
- Rationale for the selection of the starting dose: as requested by the sponsor, a starting dose of 2000 mg/kg bw test substance was chosen. The further proceeding was in accordance with the followed guideline/directive.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- According to Annex 2d of the OECD guideline and Annex 1d of the EC-Directive two groups of 3 females each were used for the stepwise dosing.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations (including but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions) were performed 0.5, 1, 2, 3, 4, and 6 hours after administration (p.a.) of the test substance and then at least once a day for a total of 2 weeks; body weights (before administration, 7 days p.a. and 14 days p.a.); and body weight gain (calculated between 0 and 7 days p.a. and between 7 and 14 days p.a.)
- Necropsy of survivors performed: yes; the animals were sacrificed by inhalation of 80 % CO2 + 20 % air 14 days p.a. and subjected to a necropsy including a gross pathological examination.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality was observed.
Mortality:
All animals survived until the scheduled termination of the study.
Clinical signs:
No abnormalities were observed during study period.
Body weight:
All animals gained weight in both weeks p.a. (Table 1).
Gross pathology:
No animal showed any abnormal finding at the necropsy 14 days p.a.

Any other information on results incl. tables

Table 1: Body weights and body weight gain

Treatment step – Dose level (mg/kg bw)

Mean body weight (g) ± SD

Deaths

Mean body weight gain (g) ± SD

Day 0

Day 7

Day 14

0-7 days

7-14 days

Step 1 – 2000

185 ± 2

215 ± 4

225 ± 4

-

29.7 ± 4.0

10 ± 6.2

Step 2 – 2000

186 ± 6

229 ±10

257 ± 31

-

43.3 ± 5.1

28.0 ±2 0.9

SD: standard deviation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met