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Administrative data

Description of key information

In a GLP-study according to OECD TG 420 (acute oral toxicity), the rat LD50 of the test substance was determined to be > 2000mg/kg bodyweight.
In a study according to a FDA guideline, the acute dermal LD50 to rabbits of the test substance was determined to be > 2000mg/kg bodyweight.

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:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Tierzucht Schönwalde GmbH
- Weight at study initiation: 136-177 g
- Fasting period before study: 18 hours
- Housing: 2-3 animals per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +- 3
- Humidity (%): 55 +- 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test article was administered orally by gavage to rats fasted for approximately 18 hours prior to dosing. After dosing diet was withheld for a further 3 hours. Dosing took place between 9.05 and 9.30 a.m.
The study was initiated with a sighting study: One female rat was given the test item in a 2000 mg/kg b.wt. dose. Slight signs of toxicity were observed in this rat.
On the basis of the results from the sighting study it was decided to carry out the main study with one group consisting of five male and five female rats given a dose of 2000 mg/kg b.wt. The dose volume administered was 10 ml/kg b.wt. both in sighting and main study.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each rat was observed 1, 3 and 6 hours after administration and thereafier daily for a period of 14 consecutive days. Body weight (b.wt.) was recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,gross pathology
Statistics:
N/A
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
2 female rats found dead on day 2
Clinical signs:
pinched abdomen observed in seven rats 1 and/or 3 hours after dosing.
Piloerection in all rats observed until day 2.
Body weight:
Mean body weight increase for males from 165g on day 0 to 236g on day 14.
Mean body weight increase for surviving females from 145g on day 0 to 186g on day 14.
Gross pathology:
One animal showed slight petechail bleeding into the small intestine.
No pathological abnormalities in all other rats, including the two females found dead.
Other findings:
none stated
Interpretation of results:
GHS criteria not met
Conclusions:
In a study according to OECD Test guideline 420 (acute oral toxicity) under GLP, the rat LD50 of the test substance was determined to be > 2000mg/kg bodyweight. At this dose level, mortality was observed in two of ten animals.
Executive summary:

The acute oral toxicity of the test substance was evaluated in a study according to OECD Test Guideline 420 under GLP.

A limit test with the test substance dose of 2000 mg/kg bodyweight was performed. The substance was applied unchanged by oral gavage to ten Wistar rats of both sexes, which were observed for 14 days post application. Two female rats were found dead on day 2. Body weights gain was not impaired, while no pathological abnormalities were present in all rats, including the two dead females.

Based on these results, the rat oral acute toxicity LD50 of the test substance was > 2000mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

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:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kuiper Rabbitry
- Weight at study initiation: 2-3 kg
- Housing: individually
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +- 5
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Clip the application site (a band around the trunk) free of hair. Abrade the skin of both groups by making longitudinal abrasions every 2-3 cm such as to penetrate the stratum corneum but not the dermis. Apply the test substance uniformly to at least 10% of the body surface (240 cm2 ) of each animal. Apply the material under 2-ply gauze then wrap the trunk of each animal in plastic sheeting to retard evaporation and keep the test substance in contact with the skin. 24 hours after application, remove the wrappings and wipe the skin to remove any remaining test substance.
Duration of exposure:
24 h
Doses:
2 g/kg b.w.
No. of animals per sex per dose:
5
Control animals:
yes, concurrent no treatment
Details on study design:
Observe the animals for at least 14 days or until signs of reversible toxicity subside whichever occurs later. Observations shall be made frequently during the day of dosing and twice daily thereafter (once in the morning and again in the late afternoon). Record the nature, onset, severity, and duration of each toxic and pharmacologic sign, such as abnormal or unusual cardiovascular, respiratory, excretory, behavioral, or other activity, as well as signs indicating an adverse effect on the centrai nervous system (paralysis, lack of coordination, staggering); pupillary reaction; and time of
death. Also, record the weight of each animal on the day·of dosing, weekly thereafter and at death.
All animals living at the termination of the observation period shall be sacrificed.
All test animals shall be subjected to a complete gross necropsy following death. All abnormalities shall be recorded. In addition, all treated skin tissue shall be subjec to histological examination.
Statistics:
N/A
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One of ten rabbits was found dead on day 4.
Clinical signs:
Dead rabbit showed dehydration before death.
All other rabbits showed same signs as the control rabbits.
Body weight:
Body weights stagnated or increased over observation period of 14 days.
Gross pathology:
no findings except in dead rabbit (friable and pale liver appearing mottled; dehydrated and very dark peritoneum: abdomial skin ahrd, cracked with sognificant erythema seen)
Other findings:
none stated
Interpretation of results:
GHS criteria not met
Conclusions:
In a study according to a FDA guideline, which is equivalent to OECD guideline 423, the acute dermal LD50 to rabbits of the test substance was determined to exceed 2000mg/kg body weight.
Executive summary:

A limit test with a dose of 2000 mg/kg bodyweight was performed. The test substance was applied unchanged under occlusive conditions for 24h to the skin of ten New Zealand White rabbits of both sexes, which were observed for 14 days post application. One rabbit was found dead on day 4. Body weights stagnated or increased, while no pathological abnormalities were present in all rabbits, except the dead rabbit.

Thus, the rabbit acute dermal toxicity LD50 of the test substance exceeded 2000mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

The acute oral toxicity of the test substance was evaluated in a study according to OECD Test Guideline 420 under GLP.

A limit test with the test substance dose of 2000 mg/kg bodyweight was performed. The substance was applied unchanged by oral gavage to ten Wistar rats of both sexes, which were observed for 14 days post application. Two female rats were found dead on day 2. Body weights gain was not impaired, while no pathological abnormalities were present in all rats, including the two dead females.

Based on these results, the rat oral acute toxicity LD50 of the test substance was > 2000mg/kg bodyweight. Therefore, the test substance is considered practically non-toxic.

The acute dermal toxicity of the registered substance has been tested in a study according to a FDA guideline.

A limit test with the test substance dose of 2000 mg/kg bodyweight was performed. The test substance was applied unchanged under occlusive conditions for 24h to the skin of ten New Zealand White rabbits of both sexes, which were observed for 14 days post application. One rabbit was found dead on day 4. Body weights stagnated or increased, while no pathological abnormalities were present in all rabbits, except the dead rabbit. Thus, the rabbit acute dermal toxicity LD50 of the test substance was > 2000mg/kg bodyweight and is therefore considered practically non-toxic.

As inhalation is no primary route of exposure, the registered substance was not tested for this endpoint.

Justification for classification or non-classification

By applying the GHS classification system for chemical substances according to Regulation (EC) 1272/2008 the registered substance has not to be labelled for its acute toxicity.