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Description of key information

A LD50 of > 5000 mg/kg bw 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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.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
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
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: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf, / Switzerland
- Age at study initiation: 10 to 12 weeks
- Weight at study initiation: Males: 216 - 246g, Females: 185-192g
- Fasting period before study: 12-18 hours
- Housing: Groups of five in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, 4132 Muttenz, Switzerland).
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, Batch 22/85 rat maintenance diet ("Kliba", Klingentalmuehle AG, Switzerland) available ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen, available ad libitum.
- Acclimation period: One week under laboratory conditions, after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 55±10
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
4% in distilled water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20mL/kg bw
Doses:
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 position, motor susceptibility, skin), gross pathology
Statistics:
The LOGIT-Model could not be applied to the observed rates of death. The toxicity was estimated without the use of a statistical model.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
0%
Clinical signs:
other: Sedation, dyspnea, curved body position, ruffled fur. All rats recovered within 2 observation days.
Gross pathology:
No macroscopic organ changes were observed.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the observations the toxicity of the test substance 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 (5000 mg/kg bw) by oral gavage followed by a 14-day observation period. Mortality did not occur. Sedation, dyspnea, curved body position, ruffled fur was observed, but all rats recovered within 2 observation days. No macroscopic organ changes were observed. Based on these 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
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
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 or test system and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf, Switzerland
- Age at study initiation: 10 to 12 weeks
- Weight at study initiation: Males: 246 - 263 g, Females: 208-260 g
- Housing: Individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, 4132 Muttenz, Switzerland).
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, Batch 22/85 rat maintenance diet ("Kliba", Klingentalmuehle AG, Kaiseraugst, Switzerland), available ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen, available ad libitum.
- Acclimation period: One week under laboratory conditions, after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 55±10
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
4% in distilled 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 20 square centimeters. On test day 1, 4 mL of the test article was applied evenly on the skin and covered with an 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 and the skin reaction was assessed according to the method of Noaks and Sanderson (Noaks, D.N. and Sanderson, D.M. "A Method for Determining the Dermal Toxicity of Pesticides". Brit. J. Industr. Med., 26, 59-64, 1969).
Duration of exposure:
24 hours under an occlusive dressing and open for an additional 14 days, because the skin was not washed when the dressing was removed.
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 and daily during days 2 - 15.
- Body weights were measured on day 1 (pre administration), 8 and 15.
- All animals were necropsied.
- Each animal had an examination for changes in appearance and behavior four times during day 1, and daily during days 2-15 (general behaviour, respiration, eye, nose, motility, body position, motor susceptibility, skin), gross pathology.
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
Based on:
test mat.
Mortality:
0%
Clinical signs:
other: Necrosis, at termination of observation, the animals had not recovered from the described local symptoms.
Gross pathology:
No macroscopic organ changes were observed
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of the test substance was estimated to be 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 administered test substance (2000 mg/kg bw). The test substance was dissolved in a 4 % CMC solution and applied on the skin and covered with an occlusive dressing for 24 hours. After 24 hours, a 14-day observation period followed. No mortality and no macroscopic organ changes were observed during this period. Necrosis was observed of which the animals did not recover before the end of the observation period. Therefore, the LD50 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 (5000 mg/kg bw) by oral gavage followed by a 14-day observation period (RCC 1985). Mortality did not occur. Sedation, dyspnea, curved body position, ruffled fur was observed, but all rats recovered within 2 observation days. No macroscopic organ changes were observed. Based on these 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 test substance (2000 mg/kg bw) (RCC 1985). The test substance was dissolved in a 4 % CMC solution and applied on the skin and covered with an occlusive dressing for 24 hours. After 24 hours, a 14-day observation period followed. No mortality and no macroscopic organ changes were observed during this period. Necrosis was observed of which the animals did not recover before the end of the observation period. Therefore, the LD50 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.

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