Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: LD50 > 16000 mg/kg bw

Acute dermal toxicity: LD50 > 2000 mg/kg bw

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:
1960
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
no guideline available
Principles of method if other than guideline:
Five groups of ten albino rats of the Sherman Wistar strain were dosed by gavage with a 25% suspension of the test substance in corn oil. Highest dose level was 16 mg/kg and observation period was 14 days.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature (range of 20 +/- 5 °C), light protected
Species:
rat
Strain:
other: Sherman Wistar
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Fasting period before study: 24 hours
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25%
- Amount of vehicle (if gavage): 4 - 64 ml/kg

MAXIMUM DOSE VOLUME APPLIED: 64 ml/kg
Doses:
1, 2, 4, 8 and 16 g/kg
No. of animals per sex per dose:
10 animals per dose (no details on sex given)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
Sex:
not specified
Dose descriptor:
LD50
Effect level:
16 000 mg/kg bw
Based on:
test mat.
Mortality:
one animal of the highest dose died, no other mortalities.
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the test article exceeds 16000 mg/kg
Executive summary:

In an oral toxicity study five groups of ten albino rats of the Sherman Wistar strain were treated with the test substance to assess its acute oral toxicity. The animals were starved for a period of twenty-four hours prior to dosing and then treated by oral gavage at dose levels of 1, 2, 4, 8 and 16 g/kg. One animal treated with 16000 mg/kg died during the course of the study, no other mortalities were reported. The LD50 of the test article was therefore set at 16000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
16 000 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
Study period:
16-NOV-2006 - 07-DEC-2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. QA statement)
Remarks:
RCC Ltd.
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: HanRcc:WIST (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Laboratory/ Animal Services, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: Males: 8 weeks, Females: 11 weeks
- Housing: IndividualIy in Makrolon type-3 cages with standard softwood bedding ("Lignocel" Schill AG, CH-4132 Muttenz)
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 48/06 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland) ad Iibitum.
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10- 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Remarks:
300
Details on dermal exposure:
TEST SITE
- % coverage: 10
- 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 h

TEST MATERIAL
- Amount applied: 2 g/kg
- Concentration (if solution): 0.5 g/mL
- Constant concentration used: yes

VEHICLE
- Amount applied: 4 mL/kg
- Lot/batch no.: 130022563006152
Duration of exposure:
24 h
Doses:
2000 mg/kg bodyweight
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: at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15.
- Frequency of weighing: on day 1 (prior to administration) and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, viability, local signs
Statistics:
No statistical analysis was used.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occurred during the study.
Clinical signs:
No systemic or local signs of toxicity were observed during the course of the study.
Body weight:
The body weight was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at the scheduled necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose of the test article after single dermal administration to rats of both sexes is greater than 2000 mg/kg body weight.
Executive summary:

In a GLP-compliant dermal toxicity study following OECD testing guideline 402, five male and five female HanRcc:WIST (SPF) rats were treated with the test substance at 2000 mg/kg by dermal application. The test item was diluted in the vehicle (PEG 300) at a concentration of 0.5 g/mL and administered at a volume of 4 mL/kg for 24 hours. The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Local signs were noted once daily from test day 2 to 15. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. No deaths occurred during the study. No systemic or local signs of toxicity were observed during the course of the study. The body weight was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at the scheduled necropsy. Therefore, the median lethal dose of the test substance after single dermal administration to rats of both sexes, observed over a period of 14 days is greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Oral acute toxicity

In an oral toxicity study pre-dating GLP five groups of ten albino rats of the Sherman Wistar strain were treated with the test substance to assess its acute oral toxicity. The animals were starved for a period of twenty-four hours prior to dosing and then treated by oral gavage at dose levels of 1, 2, 4, 8 and 16 g/kg. One animal treated with 16000 mg/kg died during the course of the study, no other mortalities were reported. Based on the results of this study, the LD50 of the test article was set at 16000 mg/kg.

Dermal acute toxicity

In a GLP-compliant dermal toxicity study following OECD testing guideline 402, five male and five female HanRcc:WIST (SPF) rats were treated with the test substance at 2000 mg/kg by dermal application. The test item was diluted in the vehicle (PEG 300) at a concentration of 0.5 g/ml and administered at a volume of 4 ml/kg for 24 hours. The animals were examined daily during the acclimatization period and mortality, viability, clinical signs, local signs and body weights were recorded during the course of the study. After the observation period (15 days) all animals were necropsied and examined macroscopically. No deaths occurred during the study. No systemic or local signs of toxicity were observed during the course of the study. The body weight was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at the scheduled necropsy. In conclusion, based on the results of this study, the median lethal dose of the test substance after single dermal administration to rats of both sexes, observed over a period of 14 days is greater than 2000 mg/kg body weight.

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for acute toxicity is not warranted under Regulation (EC) No.1272/2008.