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Administrative data

Description of key information

Acute oral toxicity: 
Key study: OECD guideline 423 and EU method B.1 tris. GLP study.
LD50 oral > 2000 mg/kg bw
Acute dermal toxicity:
Key study: OECD guideline 402 and EU method B.3. GLP study.
LD50 dermal > 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:
From January 19, 2006 to February 21, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was performed according to OECD Guideline 423 and EU method B.1 tris, with GLP.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
other: Crl: CD(SD)IGS BR.
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, D-94633 Sulzfeld.
- Age at study initiation: approximately 8 weeks at the time of administration.
- Weight at study initiation:
Animal No. 41: 182 g
Animal No. 42: 184 g
Animal No. 43: 186 g
Animal No. 44: 192 g
Animal No. 45. 178 g
Animal No. 46: 193 g
Animal No. 51: 184 g
Animal No. 52: 194 g
Animal No. 53: 187 g
Animal No. 54: 182 g
Animal No. 55: 198 g
Animal No. 56: 190 g

- Housing: Single caging in Makrolon cages type III (39 cm x 23 cm x 18 cm). Wire mesh lids. Sanitation of cages once a week.
- Diet (e.g. ad libitum): Altromin 1324 forte (Producer: Altromin GmbH, D-32791 Lage) gamma irradiated with 25 kGy 60Co, ad libitum.
- Water (e.g. ad libitum): Tap water, offered in Makrolon bottles with stainless steel canules, ad libitum.
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average of 22 ºC (continous control and recording)
- Humidity (%): Average of 48.0 % (continous control and recording)
- Photoperiod (hrs dark / hrs light): Artificial light from 6 a.m. to 6 p.m.
- Air change: 12 per hour
Route of administration:
oral: gavage
Vehicle:
other: deionised water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: a homogeneus suspension could be prepared with deionised water and water shall be used preferably, according to the guidelines.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: as no prior information on the test substance was available, a starting dose of 300 mg/kg bw was chosen. The further proceeding was in accordance with the guideline/directive.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
300 mg/kg bw: two goups of 3 animals each; 2000 mg/kg bw: two groups of 3 animals each.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
Body weights: before administration, 7 and 14 days after administration.
Clinical observations: at least one a day (Observations: 0 - 0.5, 0.5 - 1, 1 - 2, 2 - 4 and 4 - 6 hours after administration of the test substance (p.a.) and then at least once a day for a total of 2 weeks; observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions)
- Necropsy of survivors performed: yes
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived until the scheduled termination of the study.
Clinical signs:
Only the high dosed animals were affected; the findings, with an earliest onset 1 h after administration and lasting untill 6 h p.a. were: signs of reduced well-being, this term encompasses uspecific alterations like sedation, apathy, piloerection, hunched posture or closed eyes, in single or multiple occurence.
Body weight:
All animals gained weight in both weeks.
Other findings:
- Other observations:
Necropsy findings: all animals were normal at necropsy 14 days p.a.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No severe toxic effects of the test substance were noted by signs in life and post mortem at dose of 2000 mg test substance/kg bw (LD50 > 2000 mg/kg bw). No mortality occurred.
Executive summary:

Assessment of acute oral toxicity of the test substance was determined according to the OECD 423 Guideline and B.1 EU Method (Acute Toxic Class Method), with CLP. The test substance was administered once orally via gavage as a suspension in deionised water to female Crl:CD(SD)IGS BR rats. The dosing was performed sequentially to groups of 3 animals per step using a starting dose of 300 mg/kg bw and 2000 mg/kg bw as the second dose. The oral LD50 value of the test substance in rats was established to exceed 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
Klimisch 1 and the study was carried out in accordance with internationally valid GLP principles.

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:
From January 24, 2006 to February 21, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was performed according to OECD Guideline 402 and EU method B.3, with GLP.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
other: CRL: CD (SD) BR SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, D-94633 Sulzfeld.
- Age at study initiation: approximately 8 weeks (males) and 12 weeks (females) at the time of administration.
- Weight at study initiation:
Animal No. 121: 275 g
Animal No. 122: 258 g
Animal No. 123: 265 g
Animal No. 124: 246 g
Animal No. 125. 258 g
Animal No. 126: 248 g
Animal No. 127: 239 g
Animal No. 128: 226 g
Animal No. 129: 230 g
Animal No. 130: 230 g

- Housing: Single caging in Makrolon cages type III (39 cm x 23 cm x 18 cm). Wire mesh lids. Sanitation of cages once a week.
- Diet (e.g. ad libitum): Altromin 1324 forte (Producer: Altromin GmbH, D-32791 Lage) gamma irradiated with 25 kGy 60Co, ad libitum.
- Water (e.g. ad libitum): Tap water, offered in Makrolon bottles with stainless steel canules, ad libitum.
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average of 21.9 ºC (continous control and recording)
- Humidity (%): Average of 48.0 % (continous control and recording)
- Photoperiod (hrs dark / hrs light): Artificial light from 6 a.m. to 6 p.m.
- Air change: 12 per hour.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 6.5 cm x 8 cm
- % coverage: 10 % of the estimated body surface.
- Type of wrap if used: non irritating tape (Blenderm Wundpflaster, 3M)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test substance was wiped off using wet cellulose tissue, if necessary.
- Time after start of exposure: 24 hours.



Duration of exposure:
24 hours.
Doses:
Range-finding study: 400, 894 or 2000 mg/kg bw.
Main study: limit-test with one dose of 2000 mg/kg bw.
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
Body weights: before administration, 7 and 14 days after administration.
Clinical observations: at least once per day (Observations: 0 - 0.5, > 0.5 - 1, > 1 - 2, > 2 - 4 and > 4 - 6 hours after administration of the test substance (p.a.) and then at least once a day for at least 2 weeks; observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions)
- Necropsy of survivors performed: yes

Preliminary study:
In a range-finding study 3 groups of one male and one female each were dosed with 400, 894 or 2000 mg/kg bw. All animals survived for 7 days p.a. Therefore a limit-test with one dose of 2000 mg/kg bw was performed.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No local or systemic effects related to administration of the test substance were noted from clinical observations.
General findings: all animals were normal during the entire observation period.
Observation of skin condition: exposed skin was not found to be altered by the test substance.
Body weight:
All animals gained weight in both weeks.
Other findings:
- Other observations:
Staining of skin which is attributed to the staining properties of the test substance was observed in all animals.
Necropsy findings: all animals were normal at terminal necropsy.
Sex differences: No noteworthy sex difference in the response to the test substance was derived from clinical observations or post-mortem findings.

Table 1. Synopsis of the results.

Dose (mg/kg)

Sex

No. of animals

Prominent findings

exposed

affected

deceased

in life

post mortem

systemic

local

2000

male

5

0

0

none

none

none

2000

female

5

0

0

none

none

none

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No local or systemic test substance effects were noted at clinical observations or post-mortem examination at a dose of 2000 mg test substance per kg body weight. The dermal LD50 value of the test substance in rats was established to exceed 2000 mg/kg body weight.
Executive summary:

Assessment of acute dermal toxicity of the test substance was determined according to the OECD 402 Guideline and B.3 EU Method, with GLP. The test substance was administered once dermally on an area of approximately 6.5 cm x 8 cm on the dorsal thoracal region of 5 male and 5 female Sprague Dawley rats. The dose was 2000 mg/kg bw. A cellulose patch with the calculated amount of the test substance on the surface and soaked with deionised water to get optimal contact with the skin, was applied to the test site and held in place by fixing marginally with non irritating tape. Patch and tape were covered semi-occlusively by a dressing. The duration of the exposure was 24 hours. The dermal LD50 value of the test substance in rats was established to exceed 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
Klimisch 1 and the study was carried out in accordance with internationally valid GLP principles.

Additional information

Acute oral toxicity:

Key study: OECD guideline 423 and EU method B.1 tris. GLP study.

LD50 oral > 2000 mg/kg bw

Acute dermal toxicity:

Key study: OECD guideline 402 and EU method B.3. GLP study.

LD50 dermal > 2000 mg/kg bw


Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

Based on the available results, the substance is not classified for acute toxicity:

Oral LD50 > 2000 mg/kg bw: not classified.

Dermal LD50>2000 mg/kg bw: not classified.