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Administrative data

Description of key information

One oral and one dermal acute toxicity study were conducted with the test item. Both limit studies showed no mortality, no body weight change and no signs of toxicity. Therefore, the following LD50 values were determined:

oral LD50 (male/female) > 2000 mg/kg bw (reference 7.2.1 -1)

dermal LD50 (male/female) > 2000 mg/kg bw (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:
December 22, 2005 - March 31, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
96/54/EC
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001-12-17
Deviations:
no
GLP compliance:
yes
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
- Source: F. Winkelmann, 33178 Borchen
- Weight at study initiation: 157 to 179 g
- Age at study initiation: approx. 6 to 8 weeks
- Fasting period before study: Yes (Diet was withheld from 17 hours before until up to 4 hours after treatment)
- Housing: separately in type III Makrolon cages with a shelter, placed on mobile racks; conventional softwood granulate was used
- Diet: Provimi Kliba 3433.0
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22 °C
- Humidity (%): 51 to 80
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
other: Aqueous Methocel® K4M Premium solution (2.5 g/L)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 g/L
- Amount of vehicle: 10 mL/kg
- Justification for choice of vehicle: excellent vehicle performance in long range historical data

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
2000 mg/kg bw (limit test)
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs: at least 6 hours after administration and then checked daily; body weight: before treatment and 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:
Body weight: Tox-511 A
Preliminary study:
NA
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:
other: 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.
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, 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.
Executive summary:

The test item was tested for acute toxicity in rats after oral administration of 2000 mg/kg bw according to OECD TG 423 under GLP conditions. No signs of toxicity were detected in the 3 male and 3 female rats after treatment with 2000 mg/kg bw. All rats survived the observation period. Body weight development of the treated rats was inconspicuous. At necropsy no organ alterations were seen.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
OECD TG 423, GLP

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:
2007-09-10 to 2007-09-26
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:
1987-02-24
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
92/69/EC
Deviations:
no
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, DE-33178 Borchen
- Age at study initiation: approx. 9 - 10 weeks
- Weight at study initiation: 201 - 255 g
- Housing: separately
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 to 23
- Humidity (%): 44 to 70 (The humidity was transiently outside the target range of 45 to 75%. This minor and short deviation did not influence the integrity or the outcome of the study)
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Vehicle:
paraffin oil
Details on dermal exposure:
Backs and abdomens of the rats shaved with electric hair clipper, not later than 1 h before treatment.
Directly before administration test material was moistened with liquid paraffin, spread on the shaven skin, area ca. 6x6 cm, covered with gauze patch, kept in place by self-adhesive fabric. After exposure period of 24 hours gauze and adhesive fabric were removed and any remaining test material wiped off carefully.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
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 and weighing: clinical signs: at least 6 hours after administration and then checked daily; body weight: on days 2, 4, 6, 8, 11, 13, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality
Statistics:
Body weight data were recorded with the validated PC-program "AKUDAT", statistical evaluations of body weight development carried out with "TOX 511A".
Preliminary study:
NA
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the course of the study.
Clinical signs:
other: No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg.
Gross pathology:
The gross pathological examination revealed no organ alterations.
Other findings:
None.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of this study, test substance can be considered to have no acute dermal toxic potential and the expected LD50 value is higher than 2000 mg/kg bw after dermal administration to rats.
Executive summary:

No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg bw according to OECD Guideline 402 under GLP conditions. There were no deaths during the course of the study, so the lethal dose is expected to be higher than the limit dose tested. The body weight development was inconspicuous and the gross pathological examination revealed no organ alterations. Based on the results of this study, test substance can be considered to have no acute toxic potential and the expected LD50 value is higher than 2000 mg/kg bw after dermal administration to rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
OECD TG 402, GLP

Additional information

Acute oral toxicity study

In an acute oral toxicity study, one group of fasted, young adult Wistar rats (3/sex) were given a single oral dose of the test item prepared with aqueous Methocel® K4M Premium solution (2.5 g/L) as vehicle at a dose of 2000 mg/kg bw and observed for 14 days.

The oral LD50 value was determined to be:

Males > 2000 mg/kg bw

Females > 2000 mg/kg bw

Combined > 2000 mg/kg bw

No mortality occurred in this limit test.

There were no treatment related clinical signs, necropsy findings or changes in body weight (reference 7.2.1 -1).

Acute dermal toxicity study

In an acute dermal toxicity study, one group of young adult Wistar rats (5 /sex) were dermally exposed to the test item in liquid paraffin for 24 hours to the shaven body surface area of 6 x 6 cm of at a limit dose of 2000 mg/kg bw. Animals then were observed for 14 days.

The dermal LD50 value was determined to be:

Males > 2000 mg/kg bw

Females > 2000 mg/kg bw

Combined > 2000 mg/kg bw

No mortality occurred in this limit test.

No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg. No deaths occurred during the course of the study. There were no treatment related clinical signs, necropsy findings or changes in body weight (reference 7.2.3 -1).

Justification for classification or non-classification

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

The available data for acute oral and dermal toxicity are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this data, the substance is not classified for acute toxicity under Regulation (EC) No 1272/2008 (CLP), as amended for the twelfth time in Regulation (EU) 2019/521.