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Description of key information

Median lethal dose (LD50) of Reactive Red 245 in acute oral and acute dermal toxicity studies was >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:
13 Sept 1990 to 30 Oct 1990
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:
Name: FAT 40406/A
Purity: 89.3%

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 6947/14
- Expiration date of the lot/batch: July, 1995

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in the original container, protected from light at room temperature
- Stability under test conditions: stable for > 48 h
Species:
rat
Strain:
Wistar
Remarks:
Hanibm
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 start of treatment: males: 8 weeks, females, 10 weeks.
- Weight at start of treatment: males: 195 - 208 g, females: 168 - 177 g.
- Fasting period before study: 12-18 h.
- Housing: Groups of five in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet: Pelleted standard Kliba 343, Batches 73/90 and 74/90 rat maintenance diet ("Kliba" Klingentalmuehle AG, CH-4303 Kaiseraugst, available ad libitum.
- Water: Community water from Itingen, available ad libitum.
- Acclimation period: 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:
polyethylene glycol
Remarks:
PEG 400
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw at 2000 mg/kg group
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.
- Frequency of observations and weighing: Mortality / Viability: Four times during test day 1, and daily during days 2-15, Body Weights: Test days 1 (pre-administration), 8 and 15, Symptoms: Each animal was examined for changes in appearance and behavior four times during day 1, and daily during days 2-15.
- Necropsy of survivors performed: yes.
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 seen throughout the observation period.
Clinical signs:
All animals showed diarrhea only on day 1, after treatment.
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 findings were observed.
Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose (LD50) of FAT 40406/A is > 2000 mg/kg bw in Wistar rats.
Executive summary:

In a GLP compliant oral toxicity study performed according to OECD guideline 401, a group of Wistar rats (5/sex) were administered the test substance (2000 mg/kg bw) by oral gavage followed by a 14-day observation period (RCC 1990).

No mortality and macroscopical changes were observed. However, only diarrhoea was observed on day one of the observation period.

Based on the findings of the study, the median lethal dose (LD50) of FAT 40406/A is greater than 2000 mg/kg in Wistar rats.

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

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:
13 September 1990 to 18 October 1990
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 No.of test material: 6947/14
- Expiration date of the lot/batch: July, 1995

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in the original container protected from light at room temperature
- Stability under test conditions: stable for > 48 h
Species:
rat
Strain:
Wistar
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 start of treatment: males: 10 weeks, females, 12 weeks
- Weight at start of treatment: males: 224 - 243 g, females: 203 - 213 g
- Housing: Individually in Makrolon type-2 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet: Pelleted standard Kliba 343, Batches 73/90 and 74/90 rat maintenance diet ("Kliba" Klingentalmuehle AG, CH-4303 Kaiseraugst), available ad libitum.
- Water: Community water from Itingen, available ad libitum.
- Acclimation period: 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:
semiocclusive
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Details on dermal exposure:
Approximately 24 h 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, 4 mL at 2000 mg/kg test article was applied evenly on the skin with a syringe and covered with a semi-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.
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 measured four times during test day 1 (pre-administration) and daily during days 2 - 15.
- Body weights were measured on day 1, 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.
Statistics:
The LOGIT-Model could not be applied to the observed rate 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 deaths occured throughout the observation period.
Clinical signs:
The animals showed purple skin (back) during the whole study period. No systemic signs were observed.
Body weight:
The body weight gain of the animals was not affected by the test article treatment throughout the entire study.
Gross pathology:
No macroscopic organ findings were observed in the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose of FAT 40406/A is greater than 2000 mg/kg bw.
Executive summary:

In a GLP compliant dermal toxicity study performed according to OECD guideline 402, a group of Wistar rats (5/sex) were administered the test substance (2000 mg/kg bw). The test substance was dissolved in polyethylene glycol and applied on the skin with a syringe and covered with a semi-occlusive dressing for 24 h. The treated skin was washed after 24 h.

No mortality was observed during this period. No effectes were seen on body weights. Discoloration of the skin was observed during the whole study period.

Based on the study results it is concluded that, the median lethal dose (LD50) of FAT 40406/A by dermal route is greater than 2000 mg/kg in Wistar rats.

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; klimisch 1

Additional information

Acute oral toxicity:

In a GLP compliant oral toxicity study, performed according to OECD guideline 401, A group of Wistar rats (5/sex) were administered the test substance (2000 mg/kg bw) by oral gavage followed by a 14-day observation period (RCC 1990). No mortality andmacroscopical changes were observed. However, only diarrhea was observed on day one of the observation period.

Based on the study results it is concluded that, the median lethal dose (LD50) of FAT 40406/A is greater than 2000 mg/kg in Wistar rats.

Acute inhalation toxicity:

Currently no study to assess the acute inhalation toxicity potential of Reactive Red 245 is available. However, the vapour pressure for the substance can be considered low owing to the high melting point (>300 °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 liquid formulation, the exposure via inhalation is considered to be unlikely. Further, in the case 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 and dermal toxicity studies (LD50>2000 mg/kg bw), with no mortality or systemic toxicity being seen upto 2000 mg/kg bw, hence it does not need to be classified STOT SE. Taking into consideration the above arguments, low toxicity potential is expected on acute exposure of Reactive Red 245 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.

Acute dermal toxicity:

In a GLP compliant dermal toxicity study, performed according to OECD guideline 402, A group of Wistar rats (5/sex) were administered the test substance (2000 mg/kg bw) (RCC 1990). The test substance was dissolved in polyethylene glycol and applied on the skin with a syringe and covered with a semi-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 skin was observed during the whole study period. No macroscopic findings were noted. Therefore, the toxicity of the test substance was estimated to be >2000 mg/kg bw.


Justification for classification or non-classification

Based on the observed LD50 of >2000 mg/kg bw in the acute oral and dermal toxicity studies, Reactive Red 245 does not need to be classified according to according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

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