Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Jan 15 to May 22, 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Batch No. 6F11027000
- Expiration date of the lot/batch: 17.11.2016
- Purity: 96%

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 7-8 wks
- Fasting period before study: 3 hrs
- Housing: In groups of 3 animals in Tecniplast Type 2000P open cages (ca. 10% larger than Eurostandard Type IV cages)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark, artificial lighting

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 4 mL/ kg bw per gavage
- Justification for choice of vehicle: As the test item's solubility in water is poor, corn oil was used as an organic solvent. Pre­ tests showed that the solubility of the test item in corn oil was sufficient.
- Lot/batch no. (if required): Sigma, Catalogue # 1636
- Purity: 100%

CLASS METHOD
- Rationale for the selection of the starting dose: A starting dose of 2000 mg/kg bw was determined based on information from former studies on the test item (single dose LD50 < 5000 mg/kg bw)
Doses:
Planed: 2000 mg/kg, 300 mg/kg, 50 mg/kg, 5 mg/kg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: For fatalities: twice within 4h after each application, daily for remainder of observation period thereafter. For clinical signs/behavior: daily. For body weight: once before application, then weekly
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: clinical signs (behavior) and 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:
All animals survived during the planned in-life period. No animals died during the study.
Clinical signs:
All animals survived during the planned in-life period. Only one animal (E54/0) showed a slight change of behavior shortly after the application (slight lethargy, piloerection at the head, slight abnormal walk).40 minutes later this change was not detectable anymore. This observation concluded as being slight reversible change.
Body weight:
All animals showed normal weight gain for this age and strain, except for animal E54/1 of the first run, losing 4 g weight from day 8 to day 15. This weight loss concluded as being minor.
Gross pathology:
During necropsy no alterations were found. Only animal ESS/0 of the second run showed a slightly reddened thyroidea.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
according to EC 1278/2008 as amended
Conclusions:
Following the administration of a single dose of 2000 mg/kg body weight of the test item in 6 female rats, no animals died during the study and no animals showed severe suffering or moribundity. A slight reversible change of behavior was detected in one animal as well as minor weight loss in another animal. No distinct changes could be noted during necropsy. The LD50 was therefore expected to overlie 2000 mg/kg bodyweight.
Executive summary:

Following the administration of a single dose of 2000 mg/kg body weight of the test item in 6 female rats, no animals died during the study and no animals showed severe suffering or moribundity. A slight reversible change of behavior was detected in one animal as well as minor weight loss in another animal. No distinct changes could be noted during necropsy. The LD50 was therefore expected to overlie 2000 mg/kg bodyweight.