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Description of key information

The acute oral and dermal median lethal dose (LD50) of FAT 40224/C in rats of both sexes was 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
Study period:
20 November 1986 to 04 December 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material:
Op. 1/86; Vers. 10/86
- Expiration date of the lot/batch:
October 1991

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability under storage conditions:
stable; expiration: October 1991
- Stability under test conditions:
- Stability of the test substance in the solvent/dispersant/vehicle/test medium:
stable for at least 2 hours
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: 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: Pelleted standard Kliba 343, Batch 57/86 rat maintenance diet ("Kliba", Klingentalmuehle AG, 4303 Kaiseraugst, Switzerland), available ad libitum.
- Water: 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
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 1 mm.
male No. 5: lung: partly red foci, diameter 1 mm.
males No. 1,3,4: no pathologic changes.
females No. 6-10 no pathologic changes.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of FAT 40224/C in rats of both sexes was greater than 5000 mg/kg bw.
Executive summary:

In a GLP-compliant oral toxicity study, performed according to OECD guideline 401 and EU method B.1, Wistar rats (5/sex) were administered FAT 40224/C (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 (LD50) 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
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
GLP compliant guideline study

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
Study period:
20 November 1986 to 04 December 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: Op. 1/86; Vers. 10/86
- Expiration date of the lot/batch: October, 1991

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability under storage conditions: Stable
- Stability under test conditions: stable for at least 2 hours
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: 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 h
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 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 symptoms 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:
GHS criteria not met
Conclusions:
The dermal toxicity of FAT 40224/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 FAT 40224/C (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 h 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.


Based on the study results, the dermal median lethal dose (LD50) of the test substance was estimated to be: greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
GLP compliant guideline study

Additional information

Acute toxicity, oral:


In a GLP-compliant oral toxicity study, performed according to OECD guideline 401 and EU method B.1, Wistar rats (5/sex) were administered FAT 40224/C (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 (LD50) 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, inhalation:


Currently no study to assess acute inhalation toxicity of Reactive Yellow 174 is available. However, low vapour pressure owing to high melting point (>300 °C), the substance is considered to have low volatility. Synthesis of this chemical is performed in a closed process; the final product consists of non-dusty granules. Hence, the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur. Based on column 2, ‘Specific rules for adaptation from column 1’ of the table given in REACH Annex VII, the study on acute inhalation toxicity only needs to be conducted if an exposure via inhalation is to be expected, based on the likelihood of an exposure to aerosols, particles or droplets. Referring to the expected low volatility of the substance, the fact that the substance is imported into the EU in a formulated form as a dust-free powder or as a granulate, the exposure via inhalation is unlikely. The chemical showed low toxicity potential in the available acute oral (LD50 >5000 mg/kg bw) and acute dermal (LD50 >2000 mg/kg bw) with no mortality or systemic toxicity, hence, it does not need to be classified as STOT SE. Taking into consideration the above arguments, low toxicity potential is expected on acute exposure of Reactive Yellow 174 via inhalation route.


 


Acute toxicity, dermal:


In a GLP-compliant dermal toxicity study, performed according to OECD guideline 402, Wistar rats (5/sex) were administered FAT 40224/C (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 h 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. So, based on the study results, the dermal median lethal dose (LD50) of the test substance was estimated to be greater than 2000 mg/kg bw.

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 study, the test substance does not considered to be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

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