Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The acute oral LD50 of FAT 40069/A in rats is 5408 (4645 -6295) mg/kg and the acute dermal LD50 in rabbits is 5408 mg/kg (95 % confidence level 4645 - 6295).

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
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 or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 6 to 7 weeks
- Weight at study initiation: 160 to 180 g
- Fasting period before study: The rats were starved during one night before starting the treatment.
- Housing: The males and females were segregated and housed in Macrolon cages (Type 3) in groups of 5 in a room.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): approximately 50
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Details on oral exposure:
FAT 40069/A was suspended at 30 % with polyethylene glycol (PEG 400).
Doses:
-3170, 3590, 4000, 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
- Necropsy of survivors performed: yes
Statistics:
The LD50 was calculated by probit analysis method (Goulden A., Methods of Statistical Analysis, John Wiley and Sons, 1960, 3rd printing, pages 404-408).
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5 408 mg/kg bw
Based on:
test mat.
95% CL:
4 645 - 6 295
Mortality:
Yes
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. The surviving animals had recovered within 8 to 11 days. They were killed and autopsied after an observation period of 14 days.
Body weight:
None
Gross pathology:
Autopsy in dead and killed animals: No substance related gross organ changes were seen.
Other findings:
None

Mortality:

 Dose mg/kg  Concentration % of formulation     No of Animals                             Died within
     m  f  m 1hr f 1hr  m 24 hrs  f24 hrs  m 48 hrs  f 48 hrs  m 7 d f  7 d m 14 d  f 14 d
 3170  30  5  5  0  0  0  0  0  0  0  0  0
 3590  30  5  5  0  0  0  0  0  0  1  0  1
 4000  30  5  5  0
 4640  30  5  5  0  0  1  2  4  2  4  2  4
 6000  30  5  5  0  0  3
 7750  30  5  5  0  0  4
                  No higher dosed were possible                      
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of FAT 40069/A in rats of both sexes observed over a period of 14 days is 5408 mg/kg (95 % confidence level 4645-6295 mg/kg).
Executive summary:

An acute oral toxicity was determined for FAT 40069/A using Tif. RAI rats (30 males and 30 females). Before administration by oral intubation, FAT 40069/A was suspended at 30 % with polyethylene glycol (PEG 400). The test material was administered at different doses (5 males and 5 females rats per dose): 3170, 3590, 4000, 4640, 6000 and 7750 mg/kg. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnea, exophthalmos, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. The surviving animals had recovered within 8 to 11 days. They were killed and autopsied after an observation period of 14 days.At autopsy no substance related gross organ changes were seen. Mortality were seen in group of rats with dose at 3590 mg/kg body weight and above. The mortality observed was 1/10, 1/10, 6/10, 7/10 and 7/10 at 3590, 4000, 4640, 6000 and 7000 mg/kg bw, respectively. In conclusion, the acute oral LD50 of FAT 40069/A in rats of both sexes observed over a period of 14 days is 5408 mg/kg (95 % confidence level 4645-6295 mg/kg). The compound has therefore a slight acute toxicity to the rat by this route of administration.

 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 590 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Conclusions:
Data waived
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:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 434 (Acute Dermal Toxicity - Fixed Dose Procedure)
Deviations:
not specified
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 79579176, DCT # 80226
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: approximately 8 to 11 weeks
- Housing: The rabbits were individually housed in elevated wire mesh cages in temperature controlled rooms reserved exclusively for rabbits on acute tests.
- Diet (e.g. ad libitum): Purina Rabbit Chow, ad libitum
- Water (e.g. ad libitum): water from bottles were available ad libitum
- Acclimation period: The rabbits were equilibrated for at least 7 days.

Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
24 hours prior to dosing the backs of the rabbits were clipped free of fur with an Oster ANG-RA clipper head designed specifically for clipping rabbits. The rabbits were returned to their cages overnight. Just prior to dosing, the backs of even-numbered rabbits were abraded with a 21 gauge bent tip needle. The abrasions, made every 2 to 3 cm longitudinally, scratched the stratum corneum, but did not disturb the derma or produce bleeding.

Following removal of the binder at 24 hours, the test site was washed with warm tap water. One hour after washing, the test site were graded for skin irritation .

Evaluation of skin reactions:
Erythema & Eschar Formation:
- No erythema: 0
- Very slight erythema (barely perceptible): 1
- Well defined erythema: 2
- Moderate to severe erythema: 3
- Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4

Edema Formation:
- No edema: 0
- Very slight edema (barely perceptible): 1
- Slight edema (edges of area well defined by definite raising): 2
- Moderate edema (raised approximately 1 millimeter): 3
- Severe edema (raised more than 1 millimeter and extending beyond the area of exposure): 3
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
4 rabbits (2 males and 2 females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rabbits observed daily and body weight were recorded pretest and at 7 and 14 days.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight.
Preliminary study:
None
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal died at day 1 of the experiment (Animal number 3).
Clinical signs:
- Few or no feces present in pan: Animal #2, days 9-14.
- Lethargy: Animal #2, days 11-14.
- Ptosis: Animal #2, day 13.
- Yellow nasal discharge: Animal #4, days 5 & 6.
Body weight:
- Rabbit 1 (M): day 0: 1.9 kg / day 7: 2.3 kg / day 14: 2.4 kg.
- Rabbit 2 ab.(M): day 0: 2.3 kg / day 7: 2.3 kg / day 14: 2.4 kg.
- Rabbit 3 (F): day 0: 2.1 kg Dead day 1.
- Rabbit 4 ab.(F): day 0: 2.5 kg / day 7: 2.5 kg / day 14: 2.6 kg.
ab.: Abraded.
Gross pathology:
Necropsy observations:
- Animals 1&4: normal.
- Animal 2: Bloated intestines.
- Animal 3: Brown exudate, anogenital area, yellow areas on intestines, dark & mottled liver, dark areas on lungs, large spleen.

Individual body weight and skin grades:

 Rabbit number  Sex        Weights-kg
     0  7  14
 1  M  1.9 2.3  2.4 
 2 ab  M  2.3 2.3  2.4 
 3  F  2.1 Died on day 1
 4 ab  F  2.5  2.5 2.6 

ab: Abraded

       Redness        Edema
 25 h 7   14  25 h 7 14
 0  0  0  0  0
 1  1  0  0  0  0
 2  1  0  0  0  0
Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal LD50 of FAT 40069 in rabbits is greater than 2000 mg/kg bw.
Executive summary:

An acute dermal toxicity was performed for FAT 40069 in rabbits. The test was performed on New Zealand White rabbits at approximately 8 to 11 weeks of age. Twenty-four hours prior to dosing the backs of the rabbits were clipped free of fur with an Oster ANG-RA clipper head designed specifically for clipping rabbits. Just prior to dosing, the backs of even-numbered rabbits were abraded with a 21 gauge bent tip needle. The abrasions, made every 2 to 3 cm longitudinally , scratched the stratum corneum, but did not disturb the derma or produce bleeding. The test material was applied to the backs of 2 male and 2 female rabbits at a dose of 2000 mg/kg bw. The test site was covered with gauze and the trunk was wrapped with impervious material for 24 hours. Following removal of the binder at 24 hours, the test site was washed with warm tap water. One hour after washing, the test site were graded for skin irritation. Skin areas were read again at 7 and 14 days. Bodyweights were recorded pretest and at 7 and 14 days: The rabbits were observed daily for 14 days for signs of toxicity and mortality. Necropsies were performed on all rabbits. Mortality was observed in 1/4 - Animal 3, day 1. Few or no feces present in pan: Animal 2, days 9 -14. In conclusion, the acute dermal LD50 of FAT 40069 in rabbits is greater than 2000 mg/kg bw.

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

Additional information

Oral:

An acute oral toxicity was determined for FAT 40069/A using Tif. RAI rats (30 males and 30 females). Before administration by oral intubation, FAT 40069/A was suspended at 30 % with polyethylene glycol (PEG 400). The test material was administered at different doses (5 male and 5 female rats per dose): 3170, 3590, 4000, 4640, 6000 and 7750 mg/kg. 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 to 11 days. They were killed and autopsied after an observation period of 14 days. At autopsy no substance related gross organ changes were seen. Mortality were seen in group of rats with dose at 3590 mg/kg body weight and above. The mortality observed was 1/10, 1/10, 6/10, 7/10 and 7/10 at 33590, 4000, 4640, 6000 and 7000 mg/kg bw, respectively. In conclusion, the acute oral LD50 of FAT 40069/A in rats of both sexes observed over a period of 14 days is 5408mg/kg (95 % confidence level 4645-6295 mg/kg). The compound has therefore a slight acute toxicity to the rat by this route of administration.

 

Inhalation:

Currently no study to assess the acute inhalation toxicity potential of Reactive Blue 050 is available. However, the vapour pressure for the substance can be considered low owing to the high melting point (>320 °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 257 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 5408 mg/kg bw), with no mortality or systemic toxicity being seen up to 2000 mg/kg bw, hence, it does not need to be classified STOT SE and low toxicity is expected for this chemical via the inhalation route. Taking above arguments into account, low toxicity potential is expected on acute exposure of Reactive Blue 050 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.

Dermal:

Another experiment was performed to determine the potential toxicity of FAT 40069 through dermal route on rabbit skin.The test material was applied to the backs of 2 male and 2 female NZW rabbits at a dose of 2000 mg/kg. Necropsies were found on all rabbits. Only one female animal died on Day 1. 

In conclusion, the acute dermal LD50 of FAT 40069 in rabbits is greater than 2000 mg/kg.

Justification for classification or non-classification

The acute oral LD50 of FAT 40069/A in rats is 5408 (4645 -6295) mg/kg and the acute dermal LD50 in rabbits is greater than 2000 mg/kg. Hence, the test item does not meet the criteria for classification according to the Globally Harmonized Classification System.

Categories Display