Pentasodium 7-(4-(4-(5-amino-4-sulfonato-2-(4-((2-(sulfonato-ethoxy)sulfonyl)phenylazo)phenylamino)-6-chloro-1,3,5-triazin-2-yl)amino-2-ureidophenylazo)naphtalene-1,3,6-trisulfonate

Endpoint summary

Description of key information

LD50 (rat, oral, female/male) is greater than 2000 mg/kg bw.
LD50 (rat, dermal, male/female) is greater than 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:

27 October 1995 to 22 December 1995

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 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

Identification: CIBACRON GELB TZ 4210 ROH LÖSUNG (LABORGETROCKNET) (FAT 40'544/A)
Description: Red powder
Vers. No: TVi
Purity/Formulation: ca 90%
Stability of Test Article: Stable under storage condition; expiration date: NOV-2000
Storage Conditions: In the original container at room temperature away from direct sunlight.
Safety Precautions: Routine hygiene procedures were used to ensure the health and safety of the personnel.

Species:

rat

Strain:

other: Hanlbm: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd. Wölferstrasse 4, 4414 Füllinsdorf / Switzerland.
- Age at study initiation: males: 8 weeks; females: 10 weeks
- Weight at study initiation: males: 208.0 - 215.8 g; females: 180.1 - 192.4 g
- Fasting period before study: approximately 16 hours
- Housing: Groups of five in Makrol on type-4 cages with autoclaved standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: One week under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23 °C
- Humidity (%): 37 - 72 %
- Air changes (per hr): Air-conditioned with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light (approx. 100 Lux) / 12 hours dark (light period between 6.00 a.m. to 6.00 pm.), music during the light period.

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Bi-distilled

Details on oral exposure:

VEHICLE
- Amount of vehicle: 10 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg.

DOSAGE PREPARATION: The test article was placed into a glass beaker on a tared Mettler PM 480 balance, and the vehicle (bi-distilled water) was added. A weight by volume dilution was prepared using a homogenizer.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 females and 5 males per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Four times during test day 1 and daily during days 2 - 15 for mortality and viability observation. On test day 1 (pre-administration), 8 and 15 for weight observation.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight,organ weights and histopathology.

Statistics:

None

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortaility observed

Clinical signs:

other: No clinical signs of toxicity observed

Gross pathology:

No organ abnormalities were observed at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50(rat, oral) was found to be greater than 2000mg/kg.

Executive summary:

The test substance was administered to a group of 5 male and 5 female rats by oral gavage, at a single dose of 2000 mg test article/kg body weight.

The test was perfermed according to OECD test guideline 401 in a GLP certified laboratory.

The animals were observed four times during test day 1 and daily during days 2 - 15 for mortality and viability observation.

There were no deaths as a result of treatment with the test article. No clinical signs of toxicity were observed during the observation period and the body weight of the animals was within the normal range for rats of this strain and age. No organ abnormalities were observed at necropsy.

Thus, LD50 oral was greater than 2000 mg//kg bw based on the test results.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch rating 1 - GLP study.

Acute toxicity: via inhalation route

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 February 1996 to 13 May 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Identification: FAT 40549/A
Description: Yellow brown solid
Batch Number: TV 1
Stability of Test Article: Stable under storage conditions; Expiration date: 01 Jan 2001
Stability of Test Article in Vehicle: Stable in bi-distilled water for 48 hours.
Storage Conditions: In the original container at room temperature (approx. 20°C), away from direct sunlight.
Safety Precautions: Gloves, goggles and face mask were obligatory to ensure the health and safety of the personnel.

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, 4414 Füllinsdorf / Switzerland
- Age at study initiation: males: 8 weeks; females: 11 weeks
- Weight at study initiation: males: 223.5 - 245.0 g; females: 191.1 - 210.4 g
- Housing: During acclimatization in groups of five in Makrolon type-4 cages with standard softwood bedding.
- Diet: libitum
- Water: libitum
- Acclimation period: One week under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): relative humidity between 40 - 70% (values above 70% during cleaning process possible)
- Air changes (per hr): Air-conditioned with 10 - 15 air changes per hour
- Photoperiod (hrs dark / hrs light): The animals were provided with a 12-hour light, 12-hour dark cycle, with light between the hours pf 6.00 am and 6.00 pm. Music was played during the daytime light period.

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

Bi-distilled

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: 10 % of the total body surface
- Type of wrap if used: The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): lukewarm tap water
- Time after start of exposure: Twenty-four hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4.0 mL/kg body weight
- For solids, paste formed: no

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 femals and 5 males per dose

Control animals:

not specified

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 once daily during days 2 - 15.
Body Weights: On test days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs, Body weight.

Statistics:

The LOGIT-Model could not be used as no deaths occurred.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality observed

Clinical signs:

other: The clinical signs observed included orange discoloration of the skin in allanimals from test day 2 until termination of the study. Scales were observed in 1 male and 1 female animal from test day 4 to 10 and 4 to 7, respectively.

Gross pathology:

No macroscopic findings were noted at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of acute dermal toxicity test, LD50 (rat, dermal) of the test substance is estimated to be greater than 2000 mg/kg bw.

Executive summary:

The purpose of this study was to assess the acute dermal toxicity of FAT 40'549/A when administered to rats by a single semi-occlusive dermal application, followed by an observation period of 14 days.

The study procedures described in this report are based on OECD Guidelines for Testing of Chemicals, Section 4, Number 402 "Acute Dermal Toxicity", adopted February 24, 1987 and Directive 92/69/EEC, B.3. "Acute Toxicity-Dermal", July 31, 1992.

The test substance was applied to the skin of Wister rats of both sexes for 24 hrs at a dose of 2000 mg/kg bw. No mortality was observed at test concentration. No deviation from normal morphology at necropsy. The body weight gain of the animals was within the normal range for rats of this strain and age.

Therefore, the LD50 of test substance was estimated to be greater than 2000 mg/kg bw, which indicates that test substance is "not classified" in accordance with CLP (Regulaton EC No. 1272/2008) for acute dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute oral: The test substance was administered to a group of 5 male and 5 female rats by oral gavage, at a single dose of 2000 mg test article/kg body weight. The test was performed according to OECD TG 401. There were no deaths as a result of treatment with the test article. No clinical signs of toxicity were observed during the observation period and the body weight of the animals was within the normal range for rats of this strain and age. No organ abnormalities were observed at necropsy. Thus, LD50 oral was greater than 2000 mg//kg bw based on the test results.

Acute dermal: The test substance was applied to the skin of rats of both sexes for 24 hrs at a dose of 2000 mg/kg bw to access the acute toxicity. No mortality was observed at test concentration. No deviation from normal morphology at necropsy. The body weight gain of the animals was within the normal range for rats of this strain and age. Therefore, the LD50 of test substance was estimated to be greater than 2000 mg/kg bw.

Acute inhalation: Currently no study to assess the acute inhalation toxicity potential of Reactive Yellow 205 is available. The calculated value for vapour pressure was found to be <2.2E-27 Pa at 25 °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. Further the water solubility of test substance was found to be greater than 385 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: >2000 mg/kg bw), with no systemic toxicity being seen, hence it does not need to be classified STOT SE and low toxicity is expected for this chemical via the inhalation route. Taking into consideration the above arguments, low toxicity potential is expected on acute exposure of Reactive Yellow via inhalation route and hence testing by the inhalation route was considered scientifically not necessary. In addition to the oral route, for substances other than gases, the information of inhalation and dermal route shall be provided for at least one other route. The inhalation toxicity test can be waived as acute oral and dermal toxicity tests were performed.

Justification for selection of acute toxicity – oral endpoint
OECD guidance test with GLP compliance

Justification for selection of acute toxicity – dermal endpoint
OECD guidance test with GLP compliance

Justification for classification or non-classification

Based on study results, the test substance is not classified for acute oral and dermal toxicity in accordance with CLP (Regulation EC No. 1272/2008) or DSD (Directive 67/548/EEC). In addition no systemic toxicity effects were seen in the acute studies performed and thus also classification for specific target organ toxicity, single exposure is not required.

Data for acute inhalation toxicity are lacking.