Registration Dossier

Administrative data

Description of key information

The acute oral LD50 was established to be greater than 5000 mg/kg bw.

The acute dermal LD50 was > 5000 mg/kg bw 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:
1985-05-24 to 1985-06-25
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 4-6 weeks
- Weight at study initiation: male: 91-113 g, female: 102-112 g
- Housing: up to 5 animals per dose per sex in polypropylene cages
- Diet: ad libitum, no food over night before treatment and 2 h after treatment, Rat & Mouse Expanded Diet No. 1, supplied by Special Diet Services Limited, Witham, Essex
- Water: ad libitum, tap water
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 ± 2.5
- Humidity (%): 45-66
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2.5, 20, 200, 500 mg/mL
- Amount of vehicle: 10 mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL
Doses:
25, 200, 2000, 5000 mg/kg bw
No. of animals per sex per dose:
2 for range finding test, 5 for main study
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed 0.5, 1, 2, 3, 4, 5 h and afterwards once per day after treatment. The bodyweight was measured on day 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ
Statistics:
No data provided.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
One male animal (5000 mg/kg bw) died between day 2 and 3.
Clinical signs:
Hunched posture and pilo erection were observed in all rats and all dose levels. Diarrhoea was observed in single rats at 25 and 200 mg/kg bw levels. Respiratory decrease (≥ 200 mg/kg bw), lethargy and increased salvivation (≥ 2000 mg/kg bw) were observed. Starting from day 2 no clinical signs were detected.
Body weight:
No toxicological related changes were observed.
Gross pathology:
Animal that died: congestion of the lungs, ulceration and haemorrhage of glanular region of the stomach and haemorrhage of intestinal tract
Animals sacrified: No macroscopic abnormalities
Other findings:
No other observations were made.
Interpretation of results:
GHS criteria not met
Conclusions:
An acute oral toxicity study in rats was conducted. The acute oral LD50 was established to be greater than 5000 mg/kg bw.
Executive summary:

An acute oral toxicity using the standard acute method according to OECD 401 was performed with rats. 25, 200, 2000 and 5000 mg/kg bw of the test substance were administered to rats by gavage. They were observed for 14 days and afterwards sacrificed and necropsy was performed. All dose levels of the test substance produced signs of toxicity like a hunched posture and piloerection. Other signs like lethargy and increased salivation were observed for high doses only. The animals were symptom free starting from day 2 after treatment. One animal of the dose group 5000 mg/kg bw died between day 2 and 3. Due to these results the test substance was considered to be practically nontoxic and the oral LD50 > 5000 mg/kg bw was derived for rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw
Quality of whole database:
The available study is sufficient for assessment.

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
Study period:
1985-05-24 to 1985-06-24
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 10-12 weeks
- Weight at study initiation: male: 324-353 g, female: 275-286 g
- Housing: individually for 24 h after exposure; up to 5 animals per dose per sex in polypropylene cages
- Diet: ad libitum, no food over night before treatment and 2 h after treatment, Rat & Mouse Expanded Diet No. 1, supplied by Special Diet Services Limited, Witham, Essex
- Water: ad libitum, tap water
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 ± 2.5
- Humidity (%): 45-66
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: hair clipped dorsal, lateral and ventral regions (6 x 12 cm)
- % coverage: 10 % of complete body surface
- Type of wrap if used: 7 x 4 cm patch of surgical gauze, strip of elastic adhesive bandage wrapped around the trunk of the animal twice

REMOVAL OF TEST SUBSTANCE
- Washing: skin and surrounding hair were sponged thoroughly with warm water, rinsed and dried using absorbant paper
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 50 mg/kg bw (0.05 mL/kg), 400 mg/kg bw (0.43 mL/kg), 2000 mg/kg bw (2.13 mL/kg), 5000 mg/kg bw (5.32 mL/kg)
- Concentration: undiluted
- Constant volume or concentration used: yes, several animals were treated with constant concentrations and for within each concentration group a constant volume was used
Duration of exposure:
24 h
Doses:
50, 400, 2000 and 5000 mg/kg bw
No. of animals per sex per dose:
2 for range finding test, 5 for main study
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 0.5, 1, 2, 3, 4 and 5 h after application and afterwards at least once per day. The body weight was measured on day 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died.
Clinical signs:
Animals showed no observable response to treatment.
Body weight:
One female showed a small weight loss in the first week and reduced weight gain in the second week. Other animals showed normal weight gain.
Gross pathology:
No abnormalities detected.
Interpretation of results:
GHS criteria not met
Conclusions:
An acute dermal toxicity study in rats was performed. The animals showed no signs of toxicity and therefore it was concluded that the dermal LD50 was > 5000 mg/kg bw in rats.
Executive summary:

An acute dermal toxicity study in rats was performed according to OECD 402 with 50, 400, 2000 and 5000 mg/kg bw of the test substance. One female rat showed a small weight loss in the first week and reduced weight gain in the second week, while all other animals showed a normal weight gain. No mortality was observed and the animals showed no signs of toxicity. Due to these results it was concluded that the dermal LD50 was > 5000 mg/kg bw in rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw
Quality of whole database:
The available study is sufficient for assessment.

Additional information

Acute toxicity:

Oral route

An acute oral toxicity using the standard acute method according to OCED 401 was performed with rats. 25, 200, 2000 and 5000 mg/kg bw of the test substance were administered to rats by gavage. They were observed for 14 days and afterwards sacrificed and necropsy was performed. All dose levels of the test substance produced signs of toxicity like a hunched posture and piloerection. Other signs like lethargy and increased salivation were observed for high doses only. The animals were symptom free starting from day 2 after treatment. One animal of the dose group 5000 mg/kg bw died between day 2 and 3. Due to these results the test substance was considered to be practically nontoxic orally and the oral LD50 > 5000 mg/kg bw was derived for rats.

 

Dermal route

An acute dermal toxicity study in rats was performed according to OECD 402 with 50, 400, 2000 and 5000 mg/kg bw of the test substance. One female rat showed a small weight loss in the first week and reduced weight gain in the second week, while all other animals showed a normal weight gain. No mortality was observed and the animals showed no signs of toxicity. Due to these results it was concluded that the dermal LD50 was > 5000 mg/kg bw in rats.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute toxicity via oral and dermal route, the test item is not classified according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighth time in Regulation (EU) No 2016/918.