Registration Dossier

Administrative data

Description of key information

The acute oral LD50 for FAT 40061/A was found to be >7750 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:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Tif. RAI rats
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 6 to 7 weeks old
- Weight at study initiation: 160 to 180 g
-Fasting: one night before starting the treatment
- Housing: segregated and housed in Macrolon cages (Type 3)
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 50
Route of administration:
other: oral intubation
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Details on oral exposure:
Concentration % of formulation: 30 %
Doses:
- 4640, 6000 and 7750 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
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: sedation, dyspnoea, curved position and ruffled fur
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 7 750 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was seen throughout the course of the study.
Clinical signs:
Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. All animals had recovered within 7 to 8 days.
Gross pathology:
No substance-related gross organ changes were seen.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of FAT 40061/A in rats of both sexes, observed over a period of 14 days is greater than 7750 mg/kg bw.
Executive summary:

The test was performed to determine the acute oral toxicity of FAT 40061/A using a method equivalent or similar to OECD Guideline 401 (Acute Oral Toxicity). Three groups of rats, each containing 5 males and 5 females, were administered the test item at 4640, 6000 and 7750 mg/kg bw. The rats used were of 6 -7 weeks of age and weighing 160 to 180 g. No animals died during the experiment. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. All animals had recovered within 7 to 8 days. No substance related gross organ changes were seen at the autopsy. In conclusion, the acute oral LD50 of FAT 40061/A in rats of both sexes, observed over a period of 14 days is greater than 7750 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
7 750 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral:

The test was performed to determine the acute oral toxicity of FAT 40061/A using the methodology equivalent or similar to OECD Guideline 401 (Acute Oral Toxicity). Three groups of rats, each containing 5 males and 5 females, were administered the test item at 4640, 6000 and 7750 mg/kg bw. The rats used were of 6 -7 weeks of age and weighing 160 to 180 g. No animals died during the experiment. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. All animals had recovered within 7 to 8 days. No substance related gross organ changes were seen at the autopsy. In conclusion, the acute oral LD50 of FAT 40061/A in rats of both sexes, observed over a period of 14 days is greater than 7750 mg/kg bw.

 

Inhalation:

Currently no study to assess the acute inhalation toxicity potential of Reactive Yellow 039 is available. However, the vapour pressure for the substance can be considered low owing to the high melting point (>330 °C). Hence the substance is considered to have low volatility. Synthesis and spray drying 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 vapour pressure and/or 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 considered to be unlikely. Further the chemical is found to have water solubility of 197 g/L, hence in the case of dust of the substance entering the respiratory tract, it will be trapped in the mucus and cleared, thereby further limiting the absorption. The chemical showed low toxicity potential in the available acute oral toxicity study (LD50 >7750 mg/kg bw), with no mortality or systemic toxicity being seen up to 7750 mg/kg bw, hence it does not need to be classified STOT SE. Similarly, absence of systemic toxicity in skin irritation studies, further supports the conclusion that low toxicity is expected for the chemical via the inhalation route. Taking into consideration the above arguments, low toxicity potential is expected on acute exposure of Reactive Yellow 039 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.

 

Dermal:

Currently no study to assess the acute dose dermal toxicity of Reactive Yellow 039 is available. However, the molecular weight of the chemical is 699.25 g/mol, indicating it being too large for dermal absorption. It has water solubility of 197 g/L and n-octanol/water partition coefficient (log P) of -4.74, indicating it being too hydrophilic to cross the lipid rich environment of the stratum corneum. Hence, the dermal uptake for the substance will be low. The chemical showed low toxicity potential in the available acute oral toxicity study (LD50 >7750 mg/kg bw), with no mortality or systemic toxicity being seen up to 7750 mg/kg bw, hence it does not need to be classified STOT SE. Similarly, absence of systemic toxicity in skin irritation and sensitisation studies, further supports the conclusion that low toxicity is expected for the chemical via the dermal route. Further experience with similar chemical substances has demonstrated that it is very unlikely that toxicity related to the intrinsic properties of the chemical only show up upon dermal exposure and not after systemic application. Taking into consideration the above arguments, low toxicity potential is expected on acute dermal exposure of Reactive Yellow 039 and hence testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

Based on the above stated assessment of the acute oral toxicity the substance does not need to be classified for Acute Oral toxicity according to CLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council) as implementation of UN-GHS in the EU.