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Description of key information

The acute oral toxicity of the test substance in rats of both sexes, observed over a period of 14 days, was estimated to be: greater than 5000 mg/kg bw. The acute dermal toxicity of the test substance in rats of both sexes, applied to the skin for 24 hours and observed over a period of 14 days,  was estimated to be: greater than 2000 mg/kg bw.

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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.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:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf / Switzerland
- Age at study initiation: 9 - 11 weeks
- Weight at study initiation: Males: 193 - 218 g; Females: 168 - 178 g
- Fasting period before study: 12 to 18 hours (access to water was not interrupted), food was again presented approximately one hour after dosing.
- Housing: Groups of five in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, 4132 Muttenz, Switzerland). The cages were cleaned twice weekly during the test period.
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, Batch 57/86 rat maintenance diet ("Kliba", Klingentalmuehle AG, 4303 Kaiseraugst, Switzerland)
available ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen, available ad libitum.
- Acclimation period: At least 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:
CMC (carboxymethyl cellulose)
Remarks:
4% in distilled water
Details on oral exposure:
Application volume / kg body weight: 20 mL at 5000 mg/kg
Doses:
5000 mg/kg bw
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
- Mortality/viability were checked four times during test day 1, and daily during days 2-15
- Body weights were measured on test days 1 (pre-administration), 8 and 15
- All animals were necropsied.
- Each animal was examined for changes in appearance and behavior four times during day 1, and daily during days 2-15. All abnormalities were recorded. The animals were checked for the following symptoms: General behavior, Respiration, Eye, Nose, Motility, Body posture, Motor susceptibility, Skin, Loss of weight.
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:
No mortality was observed.
Clinical signs:
Sedation, dyspnea, ruffled fur.
All rats had recoverd after 2 observation days.
Body weight:
All animals showed normal body weight gain.
Gross pathology:
The following macroscopic organ changes were observed:
male No. 2: lung: several red foci, diameter 1mm.
male No. 5: lung: partly red foci, diameter 1mm.
males No. 1,3,4: no pathologic changes.
females No. 6-10 no pathologic changes.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral toxicity of FAT 40'224/C in rats of both sexes, observed over a period of 14 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) were administered the test substance (5000 mg/kg bw) by oral gavage followed by a 14-day observation period. Mortality was not observed. Symptoms observed were sedation, dyspnea and ruffled fur. All rats had recovered after 2 observation days. At necropsy 1 male showed several red foci in the lung (1 mm) and 1 male showed partly red foci in the lung (1mm). The acute oral toxicity of the test substance in rats of both sexes, observed over a period of 14 days, was estimated to be: 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: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf/Switzerland
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: Males: 200 - 228 g; Females: 182 - 201 g
- Housing: Individually in Makrolon type-2 cages with standard softwood bedding ("Lignocel", Schill AG, 4132 Muttenz/Switzerland).
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, Batch 57/86 rat maintenance diet ("Kliba", Klingentalmuehle AG, 4303 Kaiseraugst/Switzerland)
ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen, ad libitum.
- Acclimation period: At least 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:
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 10 % of the total body surface. On test day 1 the test article was applied evenly on the skin with a syringe 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.
The treated skin was washed with luke-warm tap water and dried with disposable paper towels.

Application Volume/kg body weight: 4 mL at 2000 mg/kg
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
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
- Mortality/viability were checked four times during test day 1 and daily during days 2 - 15.
- Body weights were measured on test 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. All abnormalities were recorded. The following sypmtoms were checked: General behavior, Respiration, Eye, Nose, Motility, Body position, Motor susceptibility, Skin, Loss of weight.
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:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
The application area was discolored. Discoloration of the treated skin was observed until termination of observation.
Body weight:
Emaciation (females) was observed.
Gross pathology:
No macroscopic organ changes were observed in any animal.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The toxicity of FAT 40'224/C 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 the test substance (2000 mg/kg bw). The test substance was dissolved in 4% CMC in distilled water and applied on the skin with a syringe and covered with an 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. The following symptoms were observed: Emaciation (females) and the application area was discolored. Discoloration of the treated skin was observed until termination of observation. The toxicity of the test substance was estimated to be: 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 401, Wistar rats (5/sex) were administered the test substance (5000 mg/kg bw) by oral gavage followed by a 14-day observation period (RCC 1987). Mortality was not observed. Symptoms observed were sedation, dyspnea and ruffled fur. All rats had recovered after 2 observation days. At necropsy 1 male showed several red foci in the lung (1 mm) and 1 male showed partly red foci in the lung (1 mm). The acute oral toxicity of the test substance in rats of both sexes, observed over a period of 14 days, was estimated to be: greater than 5000 mg/kg bw.

Acute toxicity, dermal:

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 1987). The test substance was dissolved in 4% CMC in distilled water and applied on the skin with a syringe and covered with an 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. The following symptoms were observed: Emaciation (females), and the application area was discolored. Discoloration of the treated skin was observed until termination of observation.The toxicity of the test substance was estimated to be 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 >5000 mg/kg bw and >2000 mg/kg bw in the acute oral and dermal toxicity studies, respectively, 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.