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Administrative data

Description of key information

acute oral toxicity, rat: LD50 > 2000 mg/kg bw

acute dermal toxicity, rat: 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:
Feb/March 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
(2001)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
Stability in the solvent was analytically proved.
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: HsdCpb:Wu
- Source: Harlan GmbH, 5960 AD Horst, Netherlands
- Age at study initiation: 8-12 weeks approximately
- Weight at study initiation: 162-186 g
- Fasting period before study: Food was withheld from the animals for approximately 16-24 h before administration of the test item, and they were fed again approximately 2-4 h after administration.
- Housing: The animals were group caged conventionally in polycarbonate cages on low dust wood granulate bedding.
- Diet and water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 5
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
Administration volume: 10 mL/kg bw

VEHICLE
Polyethylene glycol 400
Doses:
2000 mg/kg bw (single dose)
No. of animals per sex per dose:
3 for initial testing, 3 for repeat
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs and mortality rates were determined several times on the day of administration and subsequently at least once daily. The weight gain was checked weekly until the end of the study.
- Necropsy of survivors performed: yes
Statistics:
The LD50 value was estimated according to OECD TG 423 (2001).
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 5 000 mg/kg bw
Remarks on result:
other: cut-off level according to OECD TG 423, Annex 2d
Mortality:
There were no deaths.
Clinical signs:
No clinical signs were observed.
Body weight:
There were no toxicologically significant effects on body weight or body weight gain.
Gross pathology:
Necropsy performed at the end of the study revealed no particular findings.
Executive summary:

An acute oral toxicity study according OECD TG 423 was performed on 3 (initial testing) plus 3 (repeat) female rats, receiving each a single dose of 2000 mg/kg of the test item formulated in polyethylene glycol. No mortalities, no clinical signs, no effects on body weigth gain and no gross pathological findings were observed. The LD50 of the test material was estimated from the flow chart of the OECD TG 423, Annex 2d, to be >/= 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no 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
Study period:
Feb 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: HsdCpb: Wu
- Source: Harlan GmbH, 5960 AD Horst, Netherlands
- Age at study initiation: approximately 9-13 weeks
- Weight at study initiation: males 286-298 g; females 223-240 g
- Housing: The animals were caged individually in polycarbonate cages on low dust wood granulate bedding.
- Diet and water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 5
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
One day before the start of the treatment the back and flanks of the rats were shorn (approximately 10 % of the body surface area). For each dose and animal the required amount of the pure liquid test substance was calculated on the base of the body weight at time of dosing. This amount was weighed and applied as uniformly and thinly as possible to the test area, covered with a gauze-layer (6.0 cm x 5.0 cm = 30.0 cm²) of a "Cutiplast steril" coated with "Leukoflex". The gauze strip was placed on the rat's back and secured with a "Lomir biomedical Inc rat jacket", which was connected with a safety pin to the stretch tape to ensure that the animals could not ingest the test substance.

REMOVAL OF TEST SUBSTANCE
After approximately 24 hours the dressings were removed and the area was rinsed with tepid water using soap and gently patting the area dry.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw per 30.0 cm²
Dose range: males 19.1 - 19.9 mg/cm²; females 14.9 - 16.0 mg/cm².
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: at least 14 days
- Frequency of observations and weighing: Clinical signs and mortality rates were determined several times on the day of application and subsequently at least once daily. The weight gain of the animals was checked weekly until the end of the study.
- Necropsy of survivors performed: yes
Statistics:
An assessment of the LD50 was made based on the applied dose and dose-response curve, respectively.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortalities occurred.
Clinical signs:
No clinical signs were observed.
Body weight:
There were no toxicologically significant effects on body weight or body weight development in males and females.
Gross pathology:
The necropsies performed at the end of the study revealed no particular findings.
Executive summary:

An acute dermal toxicity study was performed according to OECD TG 402. For the purpose of a limit test 2000 mg/kg of the test item was applied semiocclusive on 5 male and 5 female rats for 24 hours. No mortalities, no clinical signs, no effects on weight development and no gross pathological findings were observed during the 14 -days observation period. The resulting LD50 was therefore > 2000 mg/kg bw for both sexes combined.

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

Additional information

An Acute Oral Toxicity study according to OECD 423 conducted on female rats revealed no mortalities, no clinical signs and no effects on body weight gain up to the limit dose of 2000 mg/kg bw. At necropsy no gross pathological findings were observed. The LD50 was estimated from the flow chart of the OECD TG 423, Annex 2d, to be >/= 5000 mg/kg bw.

No study on acute inhalation toxicity is available for the substance.

An Acute Dermal Toxicity study according to OECD TG 402 with a limit dose of 2000 mg/kg, applied semiocclusive on the skin of 5 male and 5 female rats for 24 hours, also revealed no mortalities, no clinical signs, no effects on body weight development and no gross pathological findings. The resulting LD50 was therefore > 2000 mg/kg bw for both sexes combined.

Justification for classification or non-classification

No classification required for acute toxicity according to Regulation (EC) No 1272/2008, Annex I.