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Administrative data

Description of key information

The LD50 observed for oral toxicity was >5000 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
Justification for type of information:
None
Qualifier:
no guideline followed
Principles of method if other than guideline:
Test substance was administered by oral intubation and animals were observed for 14 days.
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
None
Species:
rat
Strain:
other: RAI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: In house breeding
- Age at study initiation: 6-7 weeks
- Weight at study initiation: 160 - 180 g
- Fasting period before study: over night before starting the study
- Housing: The males and females were segregated and housed in Macrolon cages (Type 3) in groups of 5.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-1
- Humidity (%): 50
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
FAT 40065/A was weighed into an Erlenmeyer flask on a Mettler balance. It was suspended at 30 % with polyethylene glycol (PEG 400) and administered by oral intubation. Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.
Doses:
4640, 5000, 6000 and 7750 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: 1hr, 24 hr, 48 hr, 7 days and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, histopathology.
Statistics:
None applied
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
6 528 mg/kg bw
Based on:
test mat.
Remarks on result:
other: The LD50 was calculated by probit analysis method. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased.
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
4 640 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased.
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
6 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 3 animals died at the end of 14 days (LD30)
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
7 750 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 9 animals died at the end of 14 days (LD90)
Mortality:
3 (out of 10) and 9 (out of 10) animals died over the observation period of 14 days when treated with 6000 and 7750 mg/kg bw, respectively. No mortality was observed in animals treated with 4640 and 5000 mg/kg bw.
Clinical signs:
Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased.
Body weight:
Not observed
Gross pathology:
No substance-related gross organ changes were seen.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral LD50 of FAT 40065/A in rats of both sexes observed over a period of 14 days is 6528 (6049-7045)* mg/kg bw.
Executive summary:

The test compound FAT 40065/A was tested on 40 Tif. RAI rats (20 males/ 20 females), bred under SPF conditions to determine LD50 value at the end of 14 days.

At the beginning of the test, the animals were 6 to 7 weeks old and weighed 160 to 180 g. The males and females were segregated and housed in Macrolon cages (Type 3) in groups of 5 in a room kept at a constant temperature of 22 +/- 1 °C and a relative humidity of approximately 50 %. They received water and food ad libitum. The rats were starved during one night before starting the treatment.

FAT 40065/A was weighed into an Erlenmeyer flask on a Mettler balance. It was suspended at 30 % with polyethylene glycol (PEG 400) and administered by oral intubation. Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.

3 (out of 10) and 9 (out of 10) animals died over the observation period of 14 days when treated with 6000 and 7750 mg/kg bw, respectively. No mortality was observed in animals treated with 4640 and 5000 mg/kg bw.

Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. The surviving animals had recovered within 8 days. They were killed and autopsied after an observation period of 14 days. No substance-related gross organ changes were seen.

Based on the findings of the study, the acute oral LD50 of FAT 40065/A in rats of both sexes observed over a period of 14 days is 6528 (6049-7045) mg/kg which was calculated by probit analysis method.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw
Quality of whole database:
Good quality study with acceptable restrictions

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

Acute oral:

The test compound FAT 40065 was tested on 40 Tif. RAI rats (20 males/ 20 females), bred under SPF conditions to determine LD50 value at the end of 14 days. The acute oral LD50 of FAT 40065/A in rats of both sexes observed over a period of 14 days is 6528 (6049-7045) mg/kg bw which was calculated by probit analysis method.

Acute inhalation:

Currently no study to assess the acute inhalation toxicity potential of the target substance is available. However, the vapour pressure for the target substance is 1.32 × 10E-7 Pa at 20 °C, hence it is considered to have low volatility. The low partition coefficient of -2.17 at 20 °C, again point to poor absorption across the respiratory tract. The substance was found to have high water solubility (15100 mg/L), hence the inhaled dust may be retained within the mucus of the respiratory tract, thereby limiting the absorption. 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. Further, no systemic effects were observed in the oral toxicity study with the target substance, while mortality was observed at excessively high doses. Hence, low toxicity is expected on acute inhalation exposure of the substance and testing by the inhalation route was considered scientifically not necessary.

Acute dermal:

Currently no study to assess acute dermal toxicity of the target substance (Reactive Red 116) is available. However, the molecular weight of the substance is ≤1050.36 ≥969.45 g/mol, which indicates substance is too large for dermal absorption. Further, high water solubility (15100 mg/L) and low partition coefficient (log Pow = of -2.17 at 20 °C), indicate the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Hence, the dermal uptake for the substance is expected to be low. The substance showed low toxicity potential in the available acute oral toxicity studies (LD50 >5000 mg/kg bw). Similarly absence of systemic toxicity in skin irritation as well as sensitization studies, further supports the conclusion that no adverse effects are expected via dermal route. Further experience with similar chemical substances has demonstrated that it is very unlikely that toxicity related to the intrinsic properties of the test item only show up upon dermal exposure and not after systemic application. Hence, low toxicity is expected on acute dermal exposure of the substance and testing by the dermal route was considered scientifically not necessary.


Justification for classification or non-classification

The available data indicates the substance to be of low acute toxicity, hence it does not warrant classification according to EU CLP.