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Description of key information

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
5 male and 5 female rats in one step with two doses
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- SPF-Wistar rats, strain Winkelmann, Paderborn
- Mean body weight male: 210 - 230 g
- Mean body weight female: 190 - 210 g
- Fasting period before study: 16 hours
- Housing: animals were kept in groups of 5 male and 5 female "at random" divided in single cages
- Diet: laboratory standard diet (Altromin, Lage), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 22.5 ± 2.5 °C
- Humidity: 40 - 60 %
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
Administration by oral gavage, using a non-flexible stomach tube, as 10% suspension in 1% CMC.

VEHICLE
- Concentration in vehicle: 10 %


MAXIMUM DOSE VOLUME APPLIED:
- Dosage level 2000 mg/kg bw: 2.0 ml/100 g bw
- Dosage level 5000 mg/kg bw: 5.0 ml/100 g bw
Doses:
2000 and 5000 mg/kg bodyweight
No. of animals per sex per dose:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Male: 5000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 5000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weekly weighing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
Not applicable. No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
During the study, no mortality could be observed.
Clinical signs:
No clinical signs of toxicity were observed during the study.
Body weight:
The body weight of the surviving animals was within the range commonly recorded for animals of this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.
Interpretation of results:
other: not classified according to Regulation (EC) 1272/2008.
Conclusions:
The oral LD50 value of the test item in Wistar rats was established to exceed 5000 mg/kg body weight. Based on these results and according to the EC criteria for classification and labelling according to CLP (Regulation (EC) No. 1272/2008), the test item does not have to be classified and has no obligatory labelling requirement for oral toxicity.
Executive summary:

The test item did not show any mortality in rats up to 5000 mg/kg bodyweight and is therefore considered practically non-toxic.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, Wölferstrasse 4, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: 9 weeks for males and 12 weeks for femals
- Weight at study initiation: males 224.3 - 238.5 g, females 197.1 - 217.9 g
- Housing: Groups of 5 in Makrolon type-4 cages with standard softwood bedding, during treatment and observation individually in Makrolon type-3 cages with standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard Kliba 3433 rat maintencance diet, available ad libitum
- Water (e.g. ad libitum): Community tap water from Itingen, available ad libitum.
- Acclimation period: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 40 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12, recorded music was played for approx. 8 hours during the light period
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Approx. 10% of total body surface
- Type of wrap if used: semi occlusive dressing, wrapped around the abdomen and fixed with an elastic adhesive bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with lukewarm tap water and dried with disposable paper towels
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 6.0 ml / kg bw
- Concentration (if solution): 2000 mg/kg bw
- Constant volume or concentration used: yes
- For solids, paste formed: no
Duration of exposure:
24h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Male: Number of animals: 5
Female: Number of animals: 5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Mortality/Viability: Four times during test day 1 (day of administration) and once daily during days 2 to 15
- Body weights: on test day 1 (pre-administration), days 8 and 15
- Clinical sign: Each animal was examined for changes in appearance and behaviour four times during day 1 (day of administration), and once daily during days 2 to 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
Not applicable. No statistical analysis was used as no deaths occured
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occured during the study
Clinical signs:
No systemic or local signs of toxicity were observed during the study period
Body weight:
The body weight of the animals was within the range commonly recorded for animals of this strain and age
Gross pathology:
No macroscopic findings were observed at necropsy
Interpretation of results:
other: not classified according to Regulation (EC) 1272/2008.
Conclusions:
As no mortality occured in the acute dermal toxicity test (OECD 402), the LD50 of the test item is > 2000 mg/kg bodyweight. Based on these results and according to the EC criteria for classification and labelling according to GHS/CLP (Regulation (EC) No. 1272/2008), the test item does not have to be classified and has no obligatory labelling requirement for dermal toxicity.
Executive summary:

As no mortality occured in the acute dermal toxicity test (OECD 402), the LD50 of the test item is > 2000 mg/kg boddyweight and therefore the substance is not classified.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for classification or non-classification

Since no classification criteria according to CLP (Regulation (EC) No. 1272/2008) are fulfilled, the substance is not classified for acute toxicity, neither by the oral nor by the dermal route.

Non-classification by the inhalation route is adequate since no expsoure via the inhalation route is to be expected.