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Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

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Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that the source and the target substance have very similar physicochemical and (eco)toxicological properties because their chemical structures are nearly identical. An analogue approach has thus been employed. The target substance is the meta-isomer of the dye Reactive Blue 049, where the sulphonate group is bound at the meta-position of the aminobenzene moiety. The source chemical is the reaction mass of both the meta-isomer and the para-isomer of Reactive Blue 049.
The presence of sulphonate groups make both dyes highly water soluble and therefore less critical for human health and environmental issues. Based on their chemical similarity, similar properties are expected in both humans and the environment.

2. SOURCE AND TARGET CHEMICAL(S)
Source: Reactive Blue 49 meta/para (CAS# 72214-18-7 / EC# 276-481-8)
Target: Reactive Blue 49 meta (CAS# 72927-99-2 / EC# 277-040-2)

3. ANALOGUE APPROACH JUSTIFICATION
see attachment under 4.2 Melting point / freezing point
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 - < 5 000 mg/kg bw
Based on:
test mat.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral LD50 in rats lies between 2000 and 5000 mg/kg bw.
Executive summary:

They key study on acute oral toxicity showed that the source substance did not cause mortality in rats at 2000 mg/kg bw. At 5000 mg/kg bw however, all rats died. Therefore the acute oral LD50 in rats lies between 2000 and 5000 mg/kg bw. In the supporting study, the source substance was tested as a diluted solution. No mortality was observed at 5000 mg/kg bw.

The structurally related target substance will show the same behaviour and therefore it can be anticipated that the acute oral LD50 will be between 2000 and 5000 mg/kg bw as well.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
FAT 41001/C
Species:
rat
Strain:
other: Tif:RAIf(SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation:7-8 weeks
- Weight at study initiation: 195-223 g
- Housing: The animals were kept under conventional laboratory conditions. They were caged in groups of 5 in Macrolon cages type 4 with standardized soft wood bedding (Société Parisienne des sciures, Pantin).
- Diet (e.g. ad libitum): Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland), ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+-3
- Humidity (%):55+-15
- Air changes (per hr):approximately 15 air changes/h.
- Photoperiod (hrs dark / hrs light): 12 hours light/day
Route of administration:
oral: gavage
Vehicle:
other: distilled water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 500 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Dose level: 5000 mg/kg bw.

MAXIMUM DOSE VOLUME APPLIED:
10 mL/kg bw
Doses:
5000 mg/kg bw.
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily and on days 1, 7, 14 and at death
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, signs and symptoms, body weight, necropsies
Statistics:
From the body weights, the group means and their standard deviations were calculated.
Where feasable, the LD50 including the 95% confidence limit were computed by the logit method (J. Berkson, J.Am. Stat. Ass. 39. 357-65, 1944)
Preliminary study:
None
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Non toxic
Mortality:
No mortality occured
Clinical signs:
Dyspnoea, ruffled fur and curved body position were seen being common symptoms in acute tests. In addition a transient diarrhea was observed.
All animals recovered within 9 days.

Body weight:
No significant changes
Gross pathology:
No gross lesions were found at necropsy.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 value in rats via oral administration of test substance was found to be greater than 5000 mg/kg bw.
Executive summary:

Upon an acute oral administration and a 14 day post-treatment observation period, the following LD50 was determined:

LD50 in rats of both sexes: >5000 mg/kg bw

According to the company standard the test substance has practically no acute toxicity when administered orally to the albino rat.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
FAT 41001/D
Species:
rat
Strain:
other: Tif:RAIf(SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation:7-8 weeks
- Weight at study initiation: 178-219 g
- Housing: The animals were kept under conventional laboratory conditions. They were caged in groups of 5 in Macrolon cages type 4 with standardized soft wood bedding (Société Parisienne des sciures, Pantin).
- Diet (e.g. ad libitum): Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland), ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+-3
- Humidity (%):55+-15
- Air changes (per hr):approximately 15 air changes/h.
- Photoperiod (hrs dark / hrs light): 12 hours light/day
Route of administration:
oral: gavage
Vehicle:
other: Distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 250 and 200 mg/mL
- Amount of vehicle (if gavage): 20 and 10 mL/kg bw
- Dose levels: 5000, 2000 mg/kg bw.

MAXIMUM DOSE VOLUME APPLIED:
20 mL/kg bw
Doses:
5000, 2000 mg/kg bw.
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of clinical observations: daily
- Frequency of weighing: on days 1, 7, 14 and at death
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, signs and symptoms, body weight, necropsies
Statistics:
From the body weights, the group means and their standard deviations were calculated.
Where feasable, the LD50 including the 95% confidence limit were computed by the logit method (J. Berkson, J.Am. Stat. Ass. 39. 357-65, 1944)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 - < 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured at 2000 mg/kg bw, besides one male rat, which died due to intratracheal intubation.
At 5000 mg/kg bw all male and 3 female rats died on Day1. The remaining two female rats died on Day 2.
Clinical signs:
Dyspnoea, exophthalmus, ruffled fur and curved body position were seen, being common symptoms in acute tests. In addition, diarrhea was noted during the first two days as well as a blue staining of the eyes and extremities.
The surviving animals recovered within 10 days.
Body weight:
No significant changes were observed in surviving rats
Gross pathology:
In the high dose group all animals had a blue stained carcass. No other findings were made at necropsy.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 value in rats via oral administration of test substance was found to lie between 2000 and 5000 mg/kg bw.
Executive summary:

Upon an acute oral administration and a 14 day post-treatment observation period, the following LD50 was determined :

LD50 in rats of both sexes is between 2000 and 5000 mg/kg bw

According to the company standard the test substance has a slight acute toxicity when administered orally to the albino rat.

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

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The following information is available on the source substance:

A key study was conducted to assess the acute oral toxicity of Reactive Blue 49 (purity: 78.8%) in Wistar rats according to OECD Guideline 401 and EU Method B.1.

Groups of 10 fasted animals (5/sex/dose) received a single oral (gavage) dose of 5000 or 2000 mg/kg bw of the test substance. Parameters assessed included mortality, clinical observations, body weight and necropsy findings in all animals after a 15 d observation period.

At 5000 mg/kg bw all rats died within the first two study days. No test substance-related mortality occurred at 2000 mg/kg bw. No significant macroscopic abnormalities were seen at necropsy. Under the study conditions, the oral LD50 of the test substance was found to be > 2000 and < 5000 mg/kg bw in rats.

In another acute toxicity study with a liquid preparation of Reactive Blue 49 (purity: 26.1 % AS.) the acute oral toxicity of the test substance in rats (oral LD50) was > 5000 mg/kg bw.

Based on the data of all these studies it can be concluded that Reactive Blue 49 has a low toxicity by oral route.

The structurally related target substance will have a similar low oral toxicity.

Justification for classification or non-classification

Based on the above 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).