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Administrative data

Description of key information

A LD50 of >5000 and >2000mg/kg bw was observed in the acute oral and acute dermal toxicity study, respectively. 

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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, CH-4414 Füllinsdorf
- Age at study initiation: males: 9 weeks, females, 11 weeks
- Weight at study initiation: males: 206 - 230 g, females: 175 - 195 g
- Fasting period before study: 12-18 hours
- Housing: Groups of five in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz)
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, Batches 67/90 and 68/90 rat maintenance diet ("Kliba" Klingentalmuehle AG, CH-4303 Kaiseraugst, available ad libitum
- Water (e.g. ad libitum): Community water from Itingen, available ad libitum
- Acclimation period: One week under laboratory conditions, after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10mL/kg bw at 2000mg/kg group, 20mL/kg bw at 5000mg/kg bw group
Doses:
2000 or 5000 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: Mortality / Viability: Four times during test day 1, and daily during days 2-15, Body Weights: Test days 1 (pre-administration), 8 and 15, Symptoms: Each animal was examined for changes in appearance and behavior four times during day 1, and daily during days 2-15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (general behaviour, respiration, eye, nose, motility, body posture, motor susceptibility, skin), gross pathology
Statistics:
The LOGIT-Model could not be applied to the observed rates of death. The toxicity was estimated without use of a statistical model.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
0 % at 2000 mg/kg bw
0 % at 5000 mg/kg bw
Clinical signs:
2000 mg/kg: no clinical signs observed
5000 mg/kg: diarrhea (only observed at the first day of observation)
Body weight:
The body weight gain of the animals was not affected by the test article treatment throughout the entire study period.
Gross pathology:
No macroscopical findings were observed.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral toxicity of the test substance in rats of both sexes, observed over a period of 15 days, was estimated to be greater than 5000 mg/kg bw.
Executive summary:

In a GLP compliant oral toxicity study, performed according to OECD guideline 401, Wistar rats (5/sex/dose) were administered the test substance (2000 or 5000 mg/kg bw) by oral gavage followed by a 14-day observation period. All animals survived. Only diarrhea was observed in the highest dose group during day one of the observation period. No macroscopical changes were observed. Based on the observations, the acute oral toxicity of the test substance in rats of both sexes observed for a period of 14 days was greater than 5000 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.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, CH-4414 Füllinsdorf
- Age at study initiation: males: 9 weeks, females, 11 weeks
- Weight at study initiation: males: 218 - 243 g, females: 194 - 206 g
- Housing: Individually in Makrolon type-2 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, Batches 67/90 and 68/90 rat maintenance diet ("Kliba" Klingentalmuehle AG, CH-4303 Kaiseraugst, available ad libitum
- Water (e.g. ad libitum): Community water from Itingen, available ad libitum
- Acclimation period: One week under laboratory conditions, after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
Approximately 24 hours before treatment, the backs of the animals were shaved with an electric clipper, exposing an area of approximately 10 % of the total body surface. On test day 1, 4 mL at 2000 mg/kg test article was applied evenly on the 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. Twenty-four hours after the application, the dressing was removed. The treated skin was washed with lukewarm tap water and dried with disposable paper towels and the skin reaction was assessed.
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
- Mortality/viability were measured four times during test day 1 (pre-administration) and daily during days 2 - 15.
- Body weights were measured on day 1, 8 and 15.
- All animals were necropsied.
- Each animal had an examination for changes in appearance and behaviour four times during day 1, and daily during days 2-15. All abnormalities were recorded.
Statistics:
The LOGIT-Model could not be applied to the observed rate of death. The toxicity was estimated without use of a statistical model.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occured
Clinical signs:
- skin/fur: scales (back), skin yellow (back). Scales and discoloration were observed until termination of the study.
- No systemic symptoms were observed in the animals during the study.
Body weight:
The body weight gain of the animals was not affected by the test article treatment throughout the entire study.
Gross pathology:
No macroscopic organ findings were observed in the animals.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The toxicity of the test substance was estimated to be >2000 mg/kg bw.
Executive summary:

In a GLP compliant dermal toxicity study, performed according to OECD guideline 402, Wistar rats (5/sex) were administered the test substance (2000 mg/kg bw). The test substance was dissolved in water and applied on the skin with a syringe and covered with a semi-occlusive dressing for 24 hours. The treated skin was washed after 24 hours and a 14-day observation period followed. No mortality was observed during this period. Scales and discoloration were observed until termination of the study. No macroscopic findings were noted. Therefore, the toxicity of the test substance was estimated to be >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 oral toxicity:

In a GLP compliant oral toxicity study, performed according to OECD guideline 401, Wistar rats (5/sex/dose) were administered the test substance (2000 or 5000 mg/kg bw) by oral gavage followed by a 14-day observation period (RCC 1990). All animals survived. Only diarrhea was observed in the highest dose group during day one of the observation period. No macroscopical changes were observed. Based on the observations, the acute oral toxicity of the test substance in rats of both sexes observed for a period of 14 days was greater than 5000 mg/kg bw.

Acute dermal toxicity:

In a GLP compliant dermal toxicity study, performed according to OECD guideline 402, Wistar rats (5/sex) were administered the test substance (2000 mg/kg bw) (RCC 1990). The test substance was dissolved in water and applied on the skin with a syringe and covered with a semi-occlusive dressing for 24 hours. The treated skin was washed after 24 hours and a 14-day observation period followed. No mortality was observed during this period. Scales and discoloration were observed until termination of the study. No macroscopic findings were noted. Therefore, the toxicity of the test substance was estimated to be >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.