Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
yes
Remarks:
Animals of both groups were deprived of food before dosing during 21 hours instead of maximal 20 hours. Since this was only a slight prolongation this was considered to not have an effect on the study performance and outcome.
GLP compliance:
yes
Remarks:
Study was conducted in compliance with OECD GLP (1997).
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Batch: L-21343
- Expiration date of the lot/batch: 27 August, 2014
- Purity test date: 27 August, 2012

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature in the dark

FORM AS APPLIED IN THE TEST: The test article was dosed neat.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: Approximately 9 weeks old
- Weight at study initiation: Mean: 184 g
- Fasting period before study: Overnight prior to dosing
- Housing: Group housing of 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm) containing sterlized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage enrichment.
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiaten GmbH, Soest, Germany) ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: At least 5 days before start of treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 03 October, 2012 To: 19 October, 2012

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE: None

MAXIMUM DOSE VOLUME APPLIED: 1.107 mL/kg body weight
Doses:
2000 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for mortality were made twice daily and body weights were collected on Days 1, 8, and 15. Observations for clinical signs of toxicity were made daily.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
All animals survived for the duration of the study.
Clinical signs:
Piloerection was noted in the majority of animals on Day 1.
Body weight:
The body weight gains were considered normal.
Gross pathology:
At termination, isolated reddish foci were noted in the thymus of one female, however, no abnormalities were found in the remaining animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of the study, the oral LD50 of the test article is greater than 2000 mg/kg bodyweight.
Executive summary:

The acute oral toxicity potential of the test article was evaluated in Wistar rats. The study was performed in compliance with OECD GLP (1997). The test method was based OECD 423 (2001). The test material was dosed undiluted as delivered by the sponsor. Fasted rats (3, female) were given a single 2000 mg/kg oral dose of test article via gavage. As all animals survived that dosing, another group of 3 female rats were dosed in a similar manner in this step wise study. Observations for mortality were made twice daily and body weights were collected on Days 1, 8, and 15. Observations for clinical signs of toxicity were made daily. Necropsy was performed on all animals at termination. All animals survived for the duration of the study. Piloerection was noted in the majority of animals on Day 1. The body weight gains were considered normal. At termination, isolated reddish foci were noted in the thymus of one female, however, no abnormalities were found in the remaining animals. Based on the results of the study, the oral LD50 of the test article is greater than 2000 mg/kg bodyweight.