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Description of key information

The acute oral LD50 of FAT 40000/G in rats of both sexes observed over a period of 14 days is >2000 mg/kg bw. Similarly, the dermal LD50 was considered to be > 2000 mg/kg bw based on the available data with a structurally similar substance.

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:
1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
None
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Principles of method if other than guideline:
None
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
None
Species:
rat
Strain:
Wistar
Remarks:
SPF
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd. Wölferstrasse 4, CH-4414 Füllinsdorf
- Age at study initiation: males: 8 weeks females: 10 weeks
- Weight at study initiation: males: 199 - 209 g females: 165 - 179 g
- Fasting: overnight
- Housing: Makrolon type-3 cages (size: 22 x 37.5 x 15 cm) with standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard
- Water (e.g. ad libitum): Community tap water
- Acclimation period: One week under laboratory conditions, after veterinary examination. Only animals without any visual signs of illness were used for the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+-3 °C
- Humidity (%): 40-70 %,
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light (approx. 100 Lux) / 12 hours dark
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
bidistilled
Details on oral exposure:
None
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 anmals per dose
Control animals:
yes
Details on study design:
None
Statistics:
The LOGIT-Model could not be applied to the observed rates of death. The toxicity was estimated without use of a statistical model.
Preliminary study:
None
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred during the study period.
Clinical signs:
NO clinical signs were noted in the animals.
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 organ findings were observed.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of compound FAT 40000/G in rats is greater than 2000 mg/kg bw.
Executive summary:

The test article FAT 40000/G was administered to groups of 5 male and 5 female rats by oral gavage, at single dose of 2000 mg/kg. The following death rate was observed: 0 % at 2000 mg/kg. The acute oral toxicity of FAT 40000/G in rats of both sexes, observed over a period of 15 days, was estimated to be greater than 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

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:
1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose for cross-reference:
reference to same study
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 start of treatment: 8 to 9 weeks
- Weight at start of treatment: Males: 212 - 221 g, Females: 162-185 g
- Housing: Individually in Makrolon type-2 cages with standard softwood bedding ("Lignocel", Schill AG, 4132 Muttenz, Switzerland).
- Diet: Pelleted standard Kliba 343, Batch 77/87 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
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, 4mL of 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 lukewarm tap water and dried with disposable paper towels and the skin reaction was assessed according to the method of Noakes, 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
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 posture, motor susceptibility, skin)
Statistics:
The Logit model could not be applied to the observed rate of death. The toxicity was estimated without use of a statistical model.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
0%
Clinical signs:
The rats showed yellowish discolored skin at the application site.
Body weight:
Not specifically adressed
Gross pathology:
In two animals, several dark-red foci were observed in the lung.
Interpretation of results:
GHS criteria not met
Conclusions:
The toxicity 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 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. Discoloration of the application area was observed. In two animals several dark-red foci present in the lung were observed. Therefore, the toxicity of the test substance was estimated to be >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 study

Additional information

Acute oral toxicity:

A key study was performed for FAT 40000/G which was administered to groups of 5 male and 5 female rats by oral gavage, at single dose of 2000 mg/kg. The following death rate was observed: 0 % at 2000 mg/kg. The acute oral toxicity of FAT 40000/G in rats of both sexes, observed over a period of 15 days, was estimated to be greater than 2000 mg/kg. Several other studies conducted with different batches of the test item more or less confirmed the non-toxic behaviour of the substance. Therefore effects of different batches of the test item can be ruled out.

Several other supporting studies were also performed with following results:

LD50 - >5000 mg/kg bw

LD50 - 14530 mg/kg bw

Acute inhalation toxicity:

Currently no study to assess acute inhalation toxicity is available. However,due to the intrinsic properties of the test item (reactive yellow 095 is considered to have low volatility as the melting point >300 °C, while it has high water solubility of 366 g/L, indicating if vapours are produced will be trapped in the mucus) and the high values of the acute oral toxicity studies available, no effect beside sensitization are expected via the inhalation route. Experience with similar chemical structures demonstrated that it is very unlikely that toxicity related to intrinsic properties of the test item (beside effects of respiratory sensitization) only show up via the inhalation route and not via the oral-gastric route of exposure. Hence, the study is considered scientifically not necessary.

Acute dermal toxicity:

Currently no study to assess acute dermal toxicity of REACTIVE YELLOW 095 is available. However, REACTIVE YELLOW 175 was evaluated for the acute toxicity via dermal route.

In this GLP compliant dermal toxicity study, performed according to OECD guideline 402, Wistar rats (5/sex) were administered REACTIVE YELLOW 175 at the dose of 2000 mg/kg bw (RCC 1987). No mortality was observed during the observation period. Discoloration of the application area was observed. In two animals several dark-red foci present in the lung were observed. Therefore, the dermal LD50of the test substance was estimated to be >2000 mg/kg bw.

The molecular weight of REACTIVE YELLOW 095 is 797.1 g/mol, which indicates substance is too large for dermal absorption. The high water solubility (366 g/L) and low partition coefficient (log Pow = -5.7) of REACTIVE YELLOW 095, indicate the substance may be too hydrophilic to cross the lipid rich environment of thestratum corneum. Hence, the dermal uptake for the substance is expected to be low. Further, the absence of systemic toxicity or mortality in skin irritation as well as sensitization studies, further supports the conclusion that low acute toxicity is expected via dermal route. Taking into consideration the above discussion and the results of acute dermal toxicity with source REACTIVE YELLOW 195, no hazard is expected in case of dermal exposure of REACTIVE YELLOW 095, hence further experiments to assess dermal toxicity are not taken into account.

Justification for classification or non-classification

Based on the available data from acute toxicity studies with FAT 40000, the test substance does not meet the criteria for classification for acute toxicity according to the CLP (1272/2008) Regulation.

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