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Administrative data

Description of key information

Acute toxicity after single oral application was tested in female rats, which received 2000 mg/kg bw (2 x 3 females). All animals survived until the end of the study without showing any signs of toxicity. Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain. At necropsy, no macroscopic findings were observed. The LD50 value for acute oral toxicity is > 2000 mg/kg bw.

A single dermal application of the test item to 10 rats (5 males and 5 females) at a dose of 2000 mg/kg bw was associated with no mortality and neither clinical signs. The dermal LD50 was determined to be > 2000 mg/kg bw

The studies were carried out according to OECD guidelines 423 and 402.

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:
June 2003
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:
Adopted 17 Dec. 2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 6 to 10 weeks
- Weight at study initiation: 177 +/- 6.7 g
- Fasting period before study: yes
- Housing: transparent macrolon cages (type IV) on soft wood granulate in an air-conditioned room, 3 animals per cage
- Diet (e.g. ad libitum): ssniff R/M-H (V 1534), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 50 +/- 20 %
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 10. June To: 25. June 2003
Route of administration:
oral: gavage
Vehicle:
other: Tylose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 %
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: homogenity, stability

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION (if unusual):
the test item was suspended in tylose and distributed homogeneously by means of a magnetic stirrer

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: according to toxicity data of related compounds
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 (2 x 3 females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Symptoms: twice daily
Body weight: weekly
- Necropsy of survivors performed: yes
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred
Clinical signs:
Feces was discolored by compound one day after the administration, no symptoms of toxicity were observed
Body weight:
not impaired
Gross pathology:
no macroscopically visible changes
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of this OECD 423 study with female rats the LD50 of the test item is greater than 2000 mg/kg bw.
Executive summary:

Acute oral testing of the test item in famels rat yielded a LD50 greater than 2000 mg/kg be. After administration of 2000 mg/kg bw neither deaths nor symptoms occurred. Only the feces was discolored by the test compound on day 2 of the study. Development of body weight was not impaired. All animals were killed at the end of the observation period. They showed no macroscopically visible changes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
reliable without restriction

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:
Jun - Jul 2003
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:
Adopted July 31, 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
Adopted Feb 24, 1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 6 to 10 weeks
- Weight at study initiation:
males: 259 +/- 5.6 g
females: 223 +/- 9.3 g
- Fasting period before study:no, not required
- Housing: in transparent macrolon cages (type III) on soft wood granulate in air-conditioned room, 1 animal per cage
- Diet (e.g. ad libitum): ssniff R/M-H (V 1534), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 50 +/- 20%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 25. June To: 9. July 2003
Type of coverage:
occlusive
Vehicle:
other: moistened with tylose
Details on dermal exposure:
TEST SITE
- Area of exposure: 6x8 cm
- % coverage: 100
- Type of wrap if used: ealstic plaster bandage

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw (0.5 g test item moistend with 0.5 mL tylose)
- For solids, paste formed: yes, moistned with 0.5 mL tylose

VEHICLE
- Amount(s) applied (volume or weight with unit): tylose
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, twice daily
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study
Clinical signs:
No symptoms were observed.
The male animals showed reddish discolored skin one day after treatment, when the bandage was removed. Females showed reddish discolored skin on day 1 and 2 after treament.
Body weight:
Development of body weight was not impaired. One of five females showed a slight loss of body weight in the first study week, but body weight gain was nomalised in the second week.
Gross pathology:
no macroscopically visible changes reported
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the reesults obtained in this study the LD50 (dermal) of the test item for male and female rats is greater than 2000 mg/kg bw.
Executive summary:

The acute dermal toxicity testing of the test item yielded a LD50 > 2000 mg/kg bw in both male and femal animals. After administration of 2000 mg/kg w neither deaths nor symptoms occurred. The male animals showed reddish discolored akin one day after treatment when the bandage was removed. Females showed reddish discolored skin on day 1 and 2 after treatment. Development of body weight was not impaired in male animals. One of five females showed a slight body weigth loss in the first study week, but body weight gain normalised in the second study week. No animal showed macroscopically visible changes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
reliable without restriction

Additional information

Justification for classification or non-classification

Due to the results described in the acute oral and dermal toxicity studies (LD50oral/dermal in rats > 2000 mg/kg bw) the substance does not have to be classified as acute toxic.