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Description of key information

GLP compliant OECD 401: LD50 (oral) > 2000 mg/kg bw

GLP compliant OECD 402: 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:
Sep 17 - Oct 01, 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
92/69/EEC
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, 33178 Borchen
- Age at study initiation: 7 - 9 weeks
- Weight at study initiation: 164 (158 - 170) g
- Fasting period before study: 17 hours before dosing
- Housing: separately in Makrolon cages type III (floor area: 37.5 x 21 cm = 787.5 cm^2, height: 15 cm) placed on mobile racks
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 to 24°C
- Humidity (%): 42 to 60 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12 hours

IN-LIFE DATES: From: day 1 To: day 14
Route of administration:
oral: gavage
Vehicle:
other: aqueous Methocel® K4M Premium solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 100 g/L
- Amount of vehicle (if gavage): 20 mL
- Justification for choice of vehicle: good performance & historical data
- Lot/batch no. (if required): --
- Purity: --

MAXIMUM DOSE VOLUME APPLIED: 20 mL/ kg bw
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 (m) / 5 (f)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: days 2, 4, 6, 8, 11, 13, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Standard statistical methods have been applied for data processing.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was seen in rats treated with 2000 mg/kg bw.
Clinical signs:
Four rats showed pale feces only on day 2 of the study. All the other rats showed no signs of intoxication after treatment
Body weight:
The body weight development was inconspicuous throughout the study.
Gross pathology:
The gross pathological examination revealed no organ alterations.
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
The test material can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg after oral application to rats.
Executive summary:

Objective

The objective of the present study was to identify potential toxic effects of the test item after single oral administration to rats in a stepwise procedure.

Study design

The test material was tested for acute toxicity in rats after single oral administration of 2000 mg/kg body weight. The study was performed according to the OECD Guideline for Testing of Chemicals, No. 401, the EEC Directive 91/325 and the Annex to commission Directive 92/69EEC.

Results

No severe signs of toxicity were seen in the rats (5 males, 5 females) after treatment with 2000 mg/kg of the test item.
The body weight development of the rats was inconspicuous during the study.
There were no deaths during the course of the study.
The gross pathological examination revealed no organ alterations.

Conclusion

The test material can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg after oral application to rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
According to guideline under GLP.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
According to guideline under GLP.

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:
Jan 27 - 31, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
The study report was performed according to the OECD Guideline for testing of Chemicals, No. 402, and according to Commission Directive 92/69/EEC.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, 33178 Borchen
- Age at study initiation: 10 - 12 weeks
- Weight at study initiation: 237 g (range from 214 to 272 g).
- Fasting period before study: no
- Housing: separately in type III Makrolon cages with a shelter, placed on mobile racks
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 to 23 °C
- Humidity (%): 46 to 72 %.
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12 h

IN-LIFE DATES: From: day 1 To: day 15
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 6 x 6 cm
- % coverage: 100
- Type of wrap if used: self-adhesive fabric (Fixomull stretch, Beiersdorf).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.64 ml/kg
- Concentration (if solution): 1220 g/L
- Constant volume or concentration used: no

Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 (m) / 5 (f)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Standard statistical methods have been applied for data processing.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
The body weight development was inconspicuous. There were no deaths during the course of the study.
Body weight:
The body weight development was inconspicuous.
Gross pathology:
The gross pathological examination revealed no organ alterations.
Other findings:
No signs of toxicity were detected in the rats after treatment with 2000 mg/kg.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg after dermal application to rats.
Executive summary:

Study design

The test material was tested for acute toxicity in rats after single dermal administration of 2000 mg/kg body weight. The study was performed according to the OECD Guideline for Testing of Chemicals, No. 402, and according to Commission Directive 92/69EEC.

Results

No signs of toxicity were seen in the rats (5 males, 5 females) after treatment with 2000 mg/kg of the test item.
The body weight development of the rats was inconspicuous during the study.
There were no deaths during the course of the study.
The gross pathological examination revealed no organ alterations.

Conclusion

The test material can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg after dermal application to rats.

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

Additional information

Justification for classification or non-classification

Based on the provided information the test item is not classified for acute oral and dermal toxicity according to the EU Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures.