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Description of key information

The acute toxicity (LD50) of the test substance in rats is > 250 - < 500 mg/kg bw in males and > 100 - < 250 mg/kg bw in females after oral administration as well as > 250 - < 750 mg/kg bw in males and

> 100 - < 500 mg/kg bw in females after dermal administration (Bomann, 1989). The acute inhalation toxicity (LC50) is > 1404 mg/m3 air ( maximum technically attainable concentration) for male and female rats (Pauluhn, 1989).

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:
Jan to Feb 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Stability under test conditions: The formulation was prepared for immediate use and administration was carried out within 1 hour.
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Versuchstierzucht Winkelmann, Borchen, Germany
- Age at study initiation: 7-8 weeks (males), 10-11 weeks (females)
- Weight at study initiation: 162-180 g (males), 173-184 g (females)
- Housing: 5 animals per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): ca. 50
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Doses:
Males: 100, 250, 500, 750, 2000 mg/kg bw
Females: 100, 250, 500 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Administration volume: 5 mL/kg
- Duration of observation period following administration: 14 days
- Frequency of weighing: day 1, 4, 8 and 14
- Necropsy of survivors performed: yes
Statistics:
not specified
Sex:
male
Dose descriptor:
LD50
Effect level:
> 250 - < 500 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 100 - < 250 mg/kg bw
Based on:
test mat.
Mortality:
Males: After treatment with 100 or 250 mg/kg bw no animals died (0/5). After treatment with 500, 750 or 2000 mg/kg bw all animals died (5/5) within 1 day.
Females: After treatment with 100 mg/kg bw no animals died (0/5). After treatment with 250 or 500 mg/kg bw 4/5 or 5/5 animals died within 5 hours.
Clinical signs:
At 250 mg/kg bw and above male and female animals showed the following clinical signs: Apathy, labored breathing, staggering gait, reduced motility, partly abdominal or lateral position, partially low reflexes, lacrimation, closed palpebral fissures, salivary fluid, strong blood circulation, hairless body parts and partly piloerection. The symptoms occurred relatively quickly after the application and disappeared at the latest on the third day of the study.
Body weight:
Body weight development was normal for both sexes.
Gross pathology:
In the animals died after administration, the following gross pathological findings were recorded: Lungs blown, partly spotted; spleen pale; liver dark; stomach partly with clear or red fluid; partly in the glandular stomach ulcus-like foci, partly reddened mucous membrane or like corroded looking mucous membranes; intestinal tract filled with clear liquid.

No findings were recorded for the animals killed at the end of the follow-up period.
Other findings:
none specified
Interpretation of results:
Category 3 based on GHS criteria
Executive summary:

According to OECD TG 401 the acute oral toxicity (LD50) in rats is in the range of 250 - 500 mg/kg bw for males and in the range of 100 - 250 mg/kg bw for females. Thus, the test substance is proved to be moderately toxic under the described experimental conditions after single oral administration to rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
The study is GLP compliant and is of high quality (Klimisch score=1)

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Feb 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
traditional method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Versuchstierzucht Winkelmann, Borchen, Germany
- Age at study initiation: ca. 2-3 months
- Weight at study initiation: approx. 170-210 g
- Housing: 5 animals per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): ca. 50
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
other: polyethylene glyocol / ethanol 50/50 (v/v)
Mass median aerodynamic diameter (MMAD):
>= 1.32 - <= 1.51 µm
Geometric standard deviation (GSD):
>= 1.81 - <= 1.98
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
analytical concentrations: 131.8, 896.3, 1404.1 mg/m3 air
No. of animals per sex per dose:
control groups: 10
dose groups: 5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 2 weeks
- Frequency of observations and weighing: clinical signs were examined several times on the day of exposure and at least once daily therafter; body weights were measured before exposure, on days 3 and 7, and weekly thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: reflex measurements were made on the first post-exposure day.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1 404 mg/m³ air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: maximum technically attainable concentration
Mortality:
No animals died during exposure and post-observation period up to the maximal technical attainable concentration of 1404 mg/m3.
Clinical signs:
other: At 132 mg/m3 and above all rats showed slightly reddened noses on the exposure day. There were no signs of a concentration-dependent pronounced amplification of this effect.
Body weight:
Body weight development was normal for both sexes.
Gross pathology:
No gross pathological findings were observed.
Other findings:
The reflex measurements carried out on the first post-exposure day did not reveal any treatment-related changes.
Interpretation of results:
other: no acute hazard potential
Executive summary:

According to OECD TG 403 the acute inhalation toxicity (LC50) is > 1404 mg/m3 air ( maximum technically attainable concentration) for male and female rats. Thus, the test substance revealed no acute hazard potential under the described experimental conditions after a single 4 -hour inhalation exposure to rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study is GLP compliant and is of high quality (Klimisch score=1)

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 to Feb 1989
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
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Versuchstierzucht Winkelmann, Borchen, Germany
- Age at study initiation: 9 weeks (males), 14-16 weeks (females)
- Weight at study initiation: 208-237 g (males), 207-228 g (females)
- Housing: 1 animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): ca. 50
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
physiological saline
Details on dermal exposure:
TEST SITE
- Area of exposure: max. 5 cm x 6 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): treated skin areas were cleaned with soap and water
- Time after start of exposure: ca. 24 hours after start of exposure
Duration of exposure:
24 hours
Doses:
Males: 100, 250, 750, 2000 mg/kg bw
Females: 100, 500 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 weighing: day 1, 4, 8 and 14
- Necropsy of survivors performed: yes
Statistics:
not specified
Sex:
male
Dose descriptor:
LD50
Effect level:
> 250 - < 750 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 100 - < 500 mg/kg bw
Based on:
test mat.
Mortality:
Males: After treatment with 100 or 250 mg/kg bw 0/5 or 1/5 animals died within 2 days. After treatment with 750 or 2000 mg/kg bw all animals died (5/5) within 1 day.
Females: After treatment with 100 mg/kg bw no animals died (0/5). After treatment with 500 mg/kg bw all animals died (5/5) within 1 day.
Clinical signs:
At 250 mg/kg bw and above male and female animals showed the following clinical signs: Apathy, labored breathing and reddened eyelids. In addition, in males after 2000 mg/kg bw reflex reduction and strong blood circulation of hairless body parts were seen. The symptoms occurred relatively quickly after the application and disappeared at the latest on the second day of the study.
In both sexes also skin changes were observed in the application area, namely thickening and crusts in the affected skin areas.

Body weight:
Body weight development was normal for both sexes.
Gross pathology:
In the animals died after application, the following gross pathological findings were recorded: Liver dark; spleen pale; lungs blown, partly spotted; glandular stomach reddened, partly ulcus-like foci; occasionally stomach filled with liquid mash.

No findings were recorded for the animals killed at the end of the follow-up period.
Other findings:
none specified
Interpretation of results:
Category 3 based on GHS criteria
Executive summary:

According to OECD TG 402 the acute dermal toxicity (LD50) in rats is in the range of 250 - 750 mg/kg bw for males and in the range of 100 - 500 mg/kg bw for females. Thus, the test substance is proved to be moderately toxic under the described experimental conditions after acute dermal administration to rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
The study is GLP compliant and is of high quality (Klimisch score=1)

Additional information

According to OECD TG 401 the acute oral toxicity (LD50) in rats is in the range of 250 - 500 mg/kg bw for males and in the range of 100 - 250 mg/kg bw for females. Thus, the test substance is proved to be moderately toxic under the described experimental conditions after single oral administration to rats (Bomann, 1989).

According to OECD TG 402 the acute dermal toxicity (LD50) in rats is in the range of 250 - 750 mg/kg bw for males and in the range of 100 - 500 mg/kg bw for females. Thus, the test substance is proved to be moderately toxic under the described experimental conditions after acute dermal administration to rats (Bomann, 1989).

According to OECD TG 403 the acute inhalation toxicity (LC50) is > 1404 mg/m3 air ( maximum technically attainable concentration) for male and female rats. Thus, the test substance revealed no acute hazard potential under the described experimental conditions after a single 4 -hour inhalation exposure to rats (Pauluhn, 1989).

Justification for classification or non-classification

Acute toxicity: oral

Based on the study results on acute oral toxicity the following classification according to Annex I of Regulation (EC) No. 1272/2008 is required: Acute Tox. 3 (H301: Toxic if swallowed).

Acute toxicity: dermal

Based on the study results on acute dermal toxicity the following classification according to Annex I of Regulation (EC) No. 1272/2008 is required: Acute Tox. 3 (H311: Toxic in contact with skin).

Acute toxicity: inhalation

Based on the LC50 > 1404 mg/m3 air (no mortality at the maximum technically attainable concentration) a classification according to Regulation (EC) No. 1272/2008 (CLP) is not required.