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Administrative data

Description of key information

The acute oral LD50 was greater than 2000 mg/kg bw/d according to an OECD 423 compliant study in the rat (reference 7.2.1 -1).

The acute dermal LD50 was greater than 2000 mg/kg bw/d according to an OECD 402 compliant study in the rat (reference 7.2.3 -1).

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:
May 24 - June 08, 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
1984
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Test Animals
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: about 6 to 8 weeks
- Weight at study initiation: 150 - 192 g (mean 168 g; f & m)
- Fasting period before study: 17 hrs before dosing
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 - 23 °C
- Humidity: 52 - 70 %
- Air changes: not specified
- Photoperiod: 12 / 12 hrs dark / hrs light
Route of administration:
oral: gavage
Vehicle:
other: Methocel K4M Premium
Details on oral exposure:
The rats received the test material preparations orally by means of a stomach tube.
Doses:
The test material concentration was 100 g/L.The dose was 20 mL/kg or 2000 mg/kg bw.
No. of animals per sex per dose:
3 (m) / 3 (f)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observationsbehavoir and general condition of all rats were monitored for at lease 6 hours after the administration and then checked daily
- weighing: before treatement and on days 2, 4, 6, 8, 11, 13, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The body weight development of each rat and group was determined. The group mean value was calculated for each measurement and printed on tables.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality observed. All rats survived the observation period.
Clinical signs:
No signs of toxicity were detected in the 3 male and 3 female rats after treatment with 2000 mg/kg bw of the test item.
Body weight:
Body weight development of the treated rats was inconspicuous.
Gross pathology:
At necropsy no organ alterations were seen.
Other findings:
None

No signs of toxicity were detected in the 3 male and 3 female rats after treatment with 2000 mg/kg bw of the test item.

All rats survived the observation period. Body weight development of the treated rats was inconspicuous. At necropsy no organ alterations were seen.

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the result of this study, it is concluded, that the test item has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg bw following oral treatment in rats. According to the results of this study the test material can be allocated to ATC class 0 i.e. the LD50 value is expected to exceed 2000 mg/kg.
Executive summary:

The purpose of this assay was to provide information on possible health hazards for the test material and serve as a rational basis for risk assessment to the potential of acute oral toxicity of the test item in man.

The test material was tested for acute toxicity in rats after oral administration of 2000 mg/kg body weight. Directly before the administration the test material was prepared with aqueous Methocel K4M Premium solution as vehicle. This study was performed according to the ,,Acute toxic class method" (ATC; OECD TG 423). No signs of toxicity were detected in the 3 male and 3 female rats after treatment and no rat died. The gross pathological examination revealed no organ alterations. According to the results of this study the test material can be allocated to ATC class 0 i.e. the LD50 value is expected to exceed 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Reliability Score 1 (guideline compliant GLP study).

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:
2005-12-08 to 2006-02-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Test Animals
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: about 10 to 12 weeks
- Weight at study initiation: 202 - 259 g (mean 226 g; f & m)
- Fasting period before study: 17 hrs before dosing
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 - 23 °C
- Humidity: 46 - 72 %
- Air changes: not specified
- Photoperiod: 12 / 12 hrs dark / hrs light
Type of coverage:
occlusive
Vehicle:
other: aqua pro injectione
Details on dermal exposure:
The backs and abdomens of the rats were shaved with an electric hair clipper not later than one hour before treatment.The test material was prepared, spread on the shaven skin in an area of 6 x 6 cm, and covered with a gauze patch. This was kept in place by a self-adhesive fabric (Fixomull® stretch, Beiersdorf). The time of exposure was 24 hours. Then the gauze and adhesive fabric were removed and any remaining test material was wiped off carefully.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 (m) / 5 (f)
Control animals:
no
Details on study design:
- Observation for clinical symptoms: On the day of treatment the general condition and motility of the rats were slightly affected by the tape. It was difficult to distinguish between slight clinical findings and reactions due to fixation by the tape. The behavior and general condition of all rats were monitored for at least 6 hours after administration and then checked daily.

- Body weight: All animals were weighed before treatment and on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.

- Pathology: All rats were sacrificed at the end of the experimental part by C02-asphyxia. They were subjected to a gross pathological investigation.

- Statistics and evaluation: The body weight data were recorded with a PC-program. The body weight development of each rat and group was determined. The group mean value was calculated for each measurement and printed on tables.
Statistics:
The body weight development of each rat and group was determined. The group mean value was calculated for each measurement and printed on tables.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All rats survived the observation period. The lethal dose was regarded to be > 2000 mg/kg.
Clinical signs:
No signs of toxicity were detected in the 5 male and 5 female rats after dermal treatment with 2000 mg/kg bw.
Body weight:
The body weight development of the treated rats was inconspicuous.
Gross pathology:
At necropsy, no organ alterations were seen.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the result of this study, the test item 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:

The purpose of this assay was to provide information on possible health hazards for the test material and serve as a rational basis for risk assessment to the potential of acute dermal toxicity of the test item in man. The test material was tested for acute toxicity in 5 male and 5 female rats after dermal administration of 2000 mg/kg body weight. Directly before administration the test material was moistened with aqua pro injectione, spread on the shaven skin in an area of 6 x 6 cm, and covered with a gauze patch. This was kept in place by a self-adhesive fabric (Fixomull® stretch, Beiersdorf), The time of exposure was 24 hours. Then the gauze and adhesive fabric were removed and any remaining test material was wiped off carefully. No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg. There were no deaths during the course of the study. The body weight development was inconspicuous. The gross pathological examination revealed no organ alterations. Based on the result of this study, the test item 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:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Reliability Score 1 (guideline compliant GLP study)

Additional information

Oral route of administration

The test item was tested for acute toxicity in rats after oral administration of 2000 mg/kg body weight. This study was performed according to the "Acute toxic class method" (ATC).

No signs of toxicity were detected in the 3 male and 3 female rats after treatment and no rat died. The gross pathological examination revealed no organ alterations.

Dermal route of administration

The test item was tested for acute toxicity in 5 male and 5 female rats after dermal administration of 2000 mg/kg body weight. No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg. There were no deaths during the course of the study. The body weight development was inconspicuous.The gross pathological examination revealed no organ alterations. Based on the result of this study, the test item 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.

Summary

Based on the results of these studies, the test item has no acute toxic potential with LD50 values higher than 2000 mg/kg bw after oral and dermal application to rats.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute toxicity, the test item does not require classification for acute toxicity via the oral or dermal route according to Regulation (EC) No 1272/2008 (CLP), as amended for the twelfth time in Regulation (EU) 2019/521.