Registration Dossier

Administrative data

Description of key information

A LD50 greater than 2000 mg/kg bw was observed in both the acute oral and acute dermal toxicity study.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Remarks:
RCC Ltd, 4452 Itingen, Switzerland
Test type:
acute toxic class method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, CH-4414 Füllinsdorf / Switzerland
- Age when treated: 12-13 weeks
- Fasting period before study: approximately 18 hours
- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding ('Lignocel' Schill AG, CH-4132 Muttenz/Switzerland).
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 001/06 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland), ad libitum.
- Water: Community tap water from Füllinsdorf ad libitum.
- Acclimation period: Under laboratory conditions, after health examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
APPLICATION VOLUME: Test item dilution of 0.2 g/mL administered at a volume dosage of 10 mL/kg body weight.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 females/group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights: On test days 1 (prior to administration), 8 and 15. Clinical signs: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: All animals were killed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.
Statistics:
No statistical analysis was used.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
Hunched posture was noted in all animals from the 30-minute to the 3- or 5-hour reading. Additionally, slight to moderate ruffled fur was noted in two animals from the 1-hour to the 5-hour reading, in three animals from the 3- to the 5-hour reading and in one animal from the 30-minute to the 5-hour reading. Slight sedation was observed in three animals at the 5-hour reading. Reddish colored feces appeared in the cages at the 5-hour or 2-day examintaion and were still noted on test day 3.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the observations the median lethal dose of the test substance is greater than 2000 mg/kg body weight
Executive summary:

In a GLP compliant oral toxicity study, performed according to OECD guideline 423, Wistar rats (2 groups of 3 females) were administered the test substance (2000 mg/kg bw) by oral gavage followed by a 14-day observation period. All animals survived until the end of the study period and no changes in body weights and macroscopic findings were observed. The only clinical signs observed were hunced posture, slight to moderate ruffled fur and slight sedation up to the 5-hour reading. Furthermore, discolored feces was observed from the 5 -hour reading to test day 3. Based on the observations, the median lethal dose of the test substance in female rats observed for a period of 14 days was greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
GLP compliant guideline study, klimisch 1

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
Remarks:
RCC Ltd., 4452 Itingen, Switzerland
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, CH-4414 Füllinsdorf / Switzerland
- Age when treated: males: 7-8 weeks, females: 12-13 weeks
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. lndividually in Makrolon type-3 cages with standard softwood beddlng ('Lignocel', Schill AG, CH-4132 Muttenz) during treatment and observation.
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 001/06 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland), ad libitum,
- Water: Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: Under laboratory conditions, after health examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
One day before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10% of the total body surface. Only those animals without injury or irritation on the skin were used in the test. On test day 1, the test item was applied at a dose of 2000 mg/kg body weight evenly on the intact skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage. Application volume/kg body weight: 6 mL. 24 hours after the application the dressing was removed and the skin was flushed with lukewarm tap water and dried with disposable paper towels. Thereafter, the reaction sites were assessed. The fur of all animals was shaved on test days 9 just after the assessment of the reaction to facilitate the skin reading for the next day.
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights: On test days 1 (prior to administration), 8 and 15. Clinical signs: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. Local signs: Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: All animals were killed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.
Statistics:
No statistical analysis was used.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
No systemic signs of toxicity were observed during the study period. Orange red staining of the treated skin area produced by the test item was noted in all animals on test day 2 after removal of the dressing and on test day 3 and persisted until test day 4, 5, and 11.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The toxicity of the test substance is greater than 2000 mg/kg bw.
Executive summary:

In a GLP compliant dermal toxicity study, performed according to OECD guideline 402, Wistar rats (5/sex) were treated with the test substance (2000 mg/kg bw) by dermal application. The test substance was diluted in water, administered on the skin with a syringe and covered with a semi-occlusive dressing for 24 hours. After 24 hours the dressing was removed and the skin was flushed with lukewarm tap water. A 14-day observation period followed. No deaths occurred during the study and the body weight of the animals was within the range commonly recorded for this strain and age. No systemic signs of toxicity or macroscopic findings were observed. An orange red staining of the treated are was noted up to day 11. Based on the observations, the toxicity of the test substance is greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
GLP compliant guideline study, klimisch 1

Additional information

Acute toxicity, oral:

In a GLP compliant oral toxicity study, performed according to OECD guideline 423, Wistar rats (2 groups of 3 females) were administered the test substance (2000 mg/kg bw) by oral gavage followed by a 14-day observation period (RCC 2006). All animals survived until the end of the study period and no changes in body weights and macroscopic findings were observed. The only clinical signs observed were hunced posture, slight to moderate ruffled fur and slight sedation up to the 5-hour reading. Furthermore,discolored feces was observed from the 5 -hour reading to test day 3. Based on the observations, the median lethal dose of the test substance in female rats observed for a period of 14 days was greater than 2000 mg/kg bw.

Acute toxicity, dermal:

In a GLP compliant dermal toxicity study, performed according to OECD guideline 402, Wistar rats (5/sex) were treated with the test substance (2000 mg/kg bw) by dermal application (RCC 2006). The test substance was diluted in water, administered on the skin with a syringe and covered with a semi-occlusive dressing for 24 hours. After 24 hours the dressing was removed and the skin was flushed with lukewarm tap water. A 14-day observation period followed. No deaths occurred during the study and the body weight of the animals was within the range commonly recorded for this strain and age. No systemic signs of toxicity or macroscopic findings were observed. An orange red staining of the treated are was noted up to day 11. Based on the observations, the toxicity of the test substance is greater than 2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
Only study available.

Justification for selection of acute toxicity – dermal endpoint
Only study available.

Justification for classification or non-classification

Based on the observed LD50 of >2000 mg/kg bw in the acute oral and dermal toxicity study, the test substance does not need to be classified according to Directive 67/548/EEC and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.