Registration Dossier

Administrative data

Description of key information

Oral: EU Method B.1; rat LC50 >5000 mg/kg. Reliability = 1

Inhalation: No study available

Dermal: EU Method B.3; rat LD50 >2000 mg/kg. Reliability = 1

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:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Remarks:
The study was conducted according to guideline in effect at time of study conduct.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD® (SD) BR VAF plus
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: 98-116 g
- Fasting period before study: not reported
- Housing: groups of up to 5 rats of the same sex in metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): mean value was 55%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: 1% w/v aqueous methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50%
- Amount of vehicle (if gavage): 5.0 mL/kg body weight
- Justification for choice of vehicle: not reported

MAXIMUM DOSE VOLUME APPLIED: 10.0 mL/kg body weight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A preliminary test was carried out using a dose of 2.5 g/kg. The rationale was not reported.
Doses:
2.5 g/kg (preliminary test)
5.0 g/kg (main study)
No. of animals per sex per dose:
2/sex/dose (preliminary test)
5/sex/dose (main study)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 5 days (preliminary study); 14 days (main study)
- Frequency of observations and weighing: observation soon after dosing, at frequent intervals for the remainder of Day 1, and twice daily for the rest of the observation period. Rats were weighed on Days 1 (day of dosing), 8, and 15 (main study).
- Necropsy of survivors performed: yes (main study)
Statistics:
No statistical analyses were reported.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
There were no deaths.
Clinical signs:
Piloerection was observed in all rats within 5 minutes of dosing and throughout the remainder of Day 1. There were no other clinical signs, and recovery was complete, as judged by external appearance and behaviour, by Day 2.
Body weight:
A slightly low body weight gain was recorded for 1 male rat on Day 8. All other rats achieved anticipated body weight gains throughout the study.
Gross pathology:
Gross pathology findings were normal.
Interpretation of results:
GHS criteria not met
Conclusions:
LD50 >5000 mg/kg
Executive summary:

The test substance was then suspended in 1% aqueous methylcellulose and given as a single 5000 mg/kg oral dose by gavage to 5 male and 5 female rats. The rats were then observed for 14 days for mortality and clinical signs, and body weights were recorded on Days 1, 8, and 15. There were no deaths during the observation period. The only clinical sign was piloerection on Day 1. All but one male rat had normal body weight gain. Gross necropsy findings were normal. The acute oral LD50was greater than 5000 mg/kg.

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:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Remarks:
The study was conducted according to the test guidelines in effect at the time of study conduct.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD® (SD) BR VAF plus
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7-10 weeks
- Weight at study initiation: 200-252 g
- Fasting period before study: not reported
- Housing: individually in metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): mean value 47%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: 50X50 mm
- % coverage: 10% of total body surface
- Type of wrap if used: gauze held in place with an impermeable dressing encircled firmly around the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0 g/kg of body weight
- Concentration (if solution): 71.4% v/v in distilled water; paste, not a solution
- Constant volume or concentration used: yes; constant volume of 2.80 mL/kg
- For solids, paste formed: yes

Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5/sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: shortly after test substance administration, at frequent intervals for the remainder of Day 1, and twice daily thereafter.
- Frequency of weighing: Days 1 (day of dosing), 8, and 15
- Necropsy of survivors performed: yes
Statistics:
No statistical analyses were reported
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths were reported.
Clinical signs:
No clinical signs were reported.
Body weight:
Rats achieved anticipated body weight gains throughout the study.
Gross pathology:
Gross pathology findings were normal.
Interpretation of results:
GHS criteria not met
Conclusions:
LD50 >2000 mg/kg
Executive summary:

The test substance was suspended in water and applied to the clipped backs of male and female rats with an occlusive dressing at a dose of 2000 mg/kg of body weight. After 24 hours, the test substance was removed, and the animals were observed for 14 days. There were no deaths or other clinical signs of toxicity during the observation period. The animals gained weight normally. At necropsy, there were no abnormal findings. The acute lethal dermal dose of the test substance was found to be greater than 2000 mg/kg of body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

In the rat, the substance has low acute oral (LD50 >5000 mg/kg) and dermal (LD50 >2000 mg/kg) toxicity. 

Justification for classification or non-classification

Based on the acute oral LD50 in the rat (>5000 mg/kg) and the dermal LD50 in the rat (>2000 mg/kg) the substance does not need to be classified for acute toxicity according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.