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Administrative data

Description of key information

The test item has no acute toxic potential and thus the LD50 value is higher than 2000 mg/kg after single oral administration in rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-09-12 to 2012-01-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: 7 weeks (males), 9 weeks (females)
- Weight at study initiation: 169 g (from 151 to 198g)
- Fasting period before study: 17 hours
- Housing: air conditioned rooms, lighting 12 hours light 12 hours dark regime, single cages makrolon iii, conventional softwood granulate as bedding
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23°C
- Humidity (%): 51-82%
- Photoperiod (hrs dark / hrs light):12/12

Route of administration:
oral: gavage
Vehicle:
other: aqueous Methocel K4M Premium
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30g/L for 300mg/kg dose, 200g/L for 2000 mg/kg
- Amount of vehicle (if gavage): 10mL/kg
- Lot/batch no. (if required):DT170406, 31/11, 32/11,35/11

Doses:
300, 2000 mg/kg body weight
No. of animals per sex per dose:
300 mg/kg bw : 3 males
2000 mg/kg bw: 3 males, 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were weighed before treatment and on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured during the study
Clinical signs:
No clinical signs were observed for dose group with 300mg/kg bw
At dose group with 2000mg/kg bw one animal showed sunken flank on day 2 and 3 of experiment. It was caused by a clamped leg in the wire grid hindering the animal to have access to water and food. This effect is consequently not to be seen as treatment related.
Body weight:
Normal body weight gain for all animals in 300mg/kg bw and 2000 mg/kg bw. One animal had a reduction of body weight of 10% at day 2 and 3 of experiment. Due to a clamped leg in the cage the animal did not have access to food and water. After release of the stucked leg normal body weight gain was detected. Consequently this effect is not treatment related.
Gross pathology:
In one male animal of the high dose group red discolorations in the right lung were detected. These are acute multifocal hemorrhages initiated during the sacrifice.
Other findings:
none

Study Design

The test material was tested for acute toxicity in rats after single oral administration of 300 and 2000 mg/kg body weight, respectively. The test material was suspended in aqueous Methocel® K4M Premium solution. For regulatory requirements, prior to testing, an in vitro skin irritation study was performed to assess the irritant potential by means of the Human Skin Model Test. No corrosive potential could be detected. This study was performed according to GLP and the methods applied are fully compliant with OECD TG 423.

Results

No deaths occurred during the study.
The study was started with 300 mg/kg in 3 male rats and no signs of toxicity were seen. Subsequently, 3 male and 3 female rats were treated with 2000 mg/kg. One male rat treated with 2000 mg/kg showed sunken flank on day 2 and 3 of the experimental part. In all other rats treated with 2000 mg/kg no signs of toxicity were seen.

One male rat treated with 2000 mg/kg showed a decrease of body weight on day 2 of the experimental part. The clinical symptoms and decrease of body weight in this one male animal was considered to be not treatment related: the rat stuck with the right hind leg in the wire grid overnight from day 1 to 2. Therefore, the animal had no access to food or water during this time period. The body weight development of all other rats was inconspicuous throughout the study.

At gross pathological examination focal, red discoloration in the right lung was observed in one male rat which proved to be acute multifocal hemorrhages at histology examination.

Conclusions

Based on the result of this study, it is concluded that the test item has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg after single oral administration in rats.

Interpretation of results:
GHS criteria not met
Conclusions:
According to the study conducted this substance has no acute toxic potential by oral application. The LD50 value is higher than 2000 mg/kg bodyweight.
Executive summary:

This study was performed according to GLP and the methods applied are fully compliant with OECD TG 423. The LD50 value of the test material is higher than 2000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
GLP and Guideline conform study

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity study

The test material was tested for acute toxicity in rats after single oral administration of 300 and 2000 mg/kg body weight, respectively. This study was performed according to GLP and the methods applied are fully compliant with OECD TG 423.

No deaths occurred during the study. The study was started with 300 mg/kg in 3 male rats and no signs of toxicity were seen. Subsequently, 3 male and 3 female rats were treated with 2000 mg/kg. One male rat treated with 2000 mg/kg showed sunken flank on day 2 and 3 of the experimental part. In all other rats treated with 2000 mg/kg no signs of toxicity were seen.
One male rat treated with 2000 mg/kg showed a decrease of body weight on day 2 of the experimental part. The clinical symptoms and decrease of body weight in this one male animal was considered to be not treatment related: the rat stuck with the right hind leg in the wire grid overnight from day 1 to 2. Therefore, the animal had no access to food or water during this time period. The body weight development of all other rats was inconspicuous throughout the study.
At gross pathological examination focal, red discoloration in the right lung was observed in one male rat which proved to be acute multifocal hemorrhages at histology examinations.

Based on the result of this study, it is concluded that the test item has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg after single oral administration in rats.

Justification for classification or non-classification

Based on the provided data, the test is not classified and labelled for acute oral toxicity according to Regulation (EC) No 1272/2008.