[No public or meaningful name is available]

Endpoint summary

Description of key information

- Oral: LD50: > 2000 mg/kg bw in female rats (OECD TG 423); study "Arcelin (2010) Acute toxicity: oral"
- Dermal: LD50: > 2000 mg/kg bw in female rats (OECD TG 402); study "Arcelin (2010) Acute toxicity: dermal"

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:

Experiment start date - 19 January 2010; Experiment completion date - 11 February 2010; Study completion date - 12 March 2010.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (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: FAT 40851/A TE
Batch Number: TZ 5891 / BOP 02-09
Purity: 69.9 % all coloured components
Appearance: Orange powder
Expiry Date: July 31, 2014
Storage Conditions: At room temperature at about 20 °C

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst / The Netherlands
- Age at study initiation: 10 weeks
- Weight at study initiation: 173.1 g – 190.3 g
- Fasting period before study: Overnight prior to intubation (ca. 18-19h)
- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- Diet: Pelleted standard rat/mouse maintenance diet ad libitum (except for the overnight fasting period prior to intubation and approximately 3-4 hours post dose).
- Water: Community tap water from Füllinsdorf ad libitum.
- Acclimation period: Group 1: 19-Jan-2010 to 25-Jan-2010; Group 2: 19-Jan-2010 to 27-Jan-2010

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity: 30-70 % (values above 70 % during cleaning process possible)
- Air changes: Air-conditioned with 10-15 air changes per hour
- Photoperiod: Automatically controlled light cycle of 12 hours light and 12 hours dark, music during the daytime light period.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE:
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: Vehicle chosen after non-GLP solubility trial before the study initiation date
- Purity: Purified water prepared at Harlan Laboratories Ltd. was used as vehicle (deionised water which was processed and treated by the PURELAB Option-R unit, which links four purification technologies: reverse osmosis, adsorption, ion-exchange and photo oxidation).

MAXIMUM DOSE VOLUME APPLIED:
The animals received a single dose of the test item by oral gavage administration at 2000 mg/kg body weight after being fasted for approximately 18 to 19 hours (access to water was permitted). Food was provided again approximately 3 hours after dosing.

CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose: experience with simular substances

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females in two groups of three

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

Viability / Mortality:
Daily during the acclimatization period, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (in common with the clinical signs) and twice daily during days 2-15.

Clinical Signs:
Daily during the acclimatization period, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1, depending on the occurrence of clinical signs of toxicity. Once daily during days 2-15.

Body Weights:
On test days 1 (prior to administration), 8 and 15.

- Necropsy of survivors performed: yes.
All animals were killed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.

Statistics:

No statistical analysis was performed.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No intercurrent deaths occurred during the course of the study.

Clinical signs:

other: No clinical signs were observed throughout the entire observation period. Orange stained feces induced by the test item were noted on test days 2 and 3 for all animals.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Body weights [g]

Group 1 (2000 mg/kg bw)
Animal:	1	2	3
Day 1	186.3	173.9	173.1
Day 8	199.2	199.1	186.1
Day 15	212.4	205.5	188.1
Group 1 (2000 mg/kg bw)
Animal:	1	2	3
Day 1	183.9	173.1	190.3
Day 8	200.5	194.5	208.2
Day 15	212.9	201.8	224.9

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of test substance after single oral administration to female rats, observed over a period of 14 days, is: LD50 (female rat): greater than 2000 mg/kg bw.

Executive summary:

Acute oral toxicity of test substance was assessed using a standard acute toxic class test on rats according to OECD Guideline 423 and EU Method B.1tris under GLP. Two groups, each consisting of three female RccHan:WIST (SPF) rats, were treated with test substance by single oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was formulated in purified water at a concentration of 0.2 g/mL and administered at a dosing volume of 10 mL/kg. The animals were examined daily during the acclimatization period and mortality/viability and clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. All animals survived until the end of the study period. No clinical signs were observed during the course of the study. Orange feces were noted for all animals on test days 2 and 3. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy. The median lethal dose of test substance after single oral administration to female rats, observed over a period of 14 days was found to be greater than 2000 mg/kg bw. Based upon the classification criteria according to „Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008“ the test item test substance is not classified in respect to the acute oral toxicity study in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Good quality database with Klimisch rating 1

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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:

Experiment start date - 19 January 2010; Experiment completion date - 09 February 2010; Study completion date - 16 March 2010.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

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 40851/A TE
Batch Number: TZ 5891 / BOP 02-09
Purity: 69.9 % all coloured components
Appearance: Orange powder
Expiry Date: July 31, 2014
Storage Conditions: At room temperature at about 20 °C

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS RccHan: WIST(SPF)
- Source: Harlan Laboratories B.V. Kreuzelweg 53 5961 NM Horst / The Netherlands Postbus 6174 5960 AD Horst / The Netherlands
- Age at study initiation: Males: 9 weeks, Females: 11 weeks
- Weight at study initiation: Males 233.6 - 246.6 g ; Females: 187.9 - 209.2g
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 30/09 (Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) ad libitum.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum.
Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: Relative humidity between 30-70 % (values above 70 % during cleaning process possible)
- Air changes: Air-conditioned with 10-15 air changes per hour
- Photoperiod: Automatically controlled light cycle of 12 hours light and 12 hours dark, music during the daytime light period.

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

Deionised water which was processed and treated by the PURELAB Option-R unit, which links four purification technologies: reverse osmosis, adsorption, ion-exchange and photo oxidation.

Details on dermal exposure:

TEST SITE
- Area of exposure: back of the animals
- % coverage: approx. 10 % of the body surface
- Type of wrap if used: skin with a syringe and covered with a surgical gauze pad (ca. 5 x 5 cm) held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and an elastic adhesive restrainer bandage wrapped around the abdomen.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, flushed with lukewarm water and dropped off with disposable paper towels.
- Time after start of exposure: 24h

TEST MATERIAL AND VEHICLE
- Amount(s) applied (volume or weight with unit): 6mL/kg
- Concentration (if solution): dose: 2000 mg/kg BW
- Constant volume or concentration used: yes
- Test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle was added (weight: volume).

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Viability / Mortality: Daily during the acclimatization period, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.

Clinical Signs: Daily during the acclimatization period, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15.

Local Dermal Signs: Once daily during days 2 (following dressing removal) through day 15 using the numerical scoring system described in Appendix I.

Body Weights: On test days 1 (prior to administration), 8 and 15.

- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examinations were performed. An external examination and opening of the abdominal and thoracic cavities for examinations of major organs were performed. The appearance of any macroscopic abnormalities was recorded. No organs or tissues were retained.

Statistics:

No statistical analysis was used.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No intercurrent deaths occurred during the course of the study.

Clinical signs:

other: No clinical signs were recorded throughout the complete observation period.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Other findings:

Local Dermal Signs
Orange staining of the treated skin caused by the test item was observed in all animals from test day 2 up to test days 7 or 9. Otherwise, no local dermal signs were recorded in any of the animals until the end of the observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of FAT 40851/A after single dermal administration to rats of both sexes, observed over a period of 14 days, is: LD50 (rat): greater than 2000 mg/kg bw.

Executive summary:

Five male and five female RccHan:WIST (SPF) rats were treated with FAT 40851/A at 2000 mg/kg by dermal application in accordance with EU Method B.3 and under GLP conditions. The test item was formulated in purified water at a concentration of 0.33 g/mL and administered at a volume dosage of 6 mL/kg. The application period was 24 hours. The animals were examined daily during the acclimatisation period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after treatment start on test day 1 and once daily during test days 2-15. Local signs were noted once daily from test day 2 to 15. Mortality/viability was recorded within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. No intercurrent deaths occurred during the course of the study. No clinical signs were recorded throughout the complete observation period. Orange staining of the treated skin caused by the test item was observed in all animals from test day 2 up to test days 7 or 9. Otherwise, no local dermal signs were recorded in any of the animals until the end of the observation period. The body weight of all animals was considered to be within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy. The median lethal dose of FAT 40851/A after single dermal administration to rats of both sexes, observed over a period of 14 days, is: LD50 (rat): greater than 2000 mg/kg bw. Based upon the classification criteria according to the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, FAT 40851/A does not have to be classified with respect to acute dermal toxicity in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Good quality database with Klimisch rating 1

Additional information

Acute oral toxicity:

A LD50 oral (gavage, RccHan:WIST (SPF) rats) of >2000 mg/kg bw in female rats is reported for FAT 40851/A in the key study Arcelin (2010) Acute toxicity: oral" with a reliability score of 1 conducted according to OECD TG 423. No fatalities occurred, body weight development was normal. No clinical signs were observed during the course of the study. Orange faeces were noted for all animals on test days 2 and 3. However, this colouration was most likely produced by the test item and was completely reversed by test day 4. No macroscopic findings were recorded at necropsy. Accordingly the substance does not need to be classified for acute oral toxicity.

 

Acute dermal toxicity:

A LD50 dermal (semiocclusive for 24 h, RccHan:WIST (SPF) rats) of >2000 mg/kg bw in male and female rats is reported for FAT 40851/A TE in the key study Arcelin (2010) Acute toxicity: dermal" with a reliability score of 1 conducted according to OECD TG 402. No fatalities occurred, body weight development was normal. No clinical signs were recorded throughout the complete observation period. Orange staining of the treated skin caused by the test item was observed in all animals from test day 2 up to test days 7 or 9. Otherwise, no local dermal signs were recorded in any of the animals until the end of the observation period. Accordingly the substance does not need to be classified for acute dermal toxicity.

 

Acute inhalation toxicity:

Currently no study to assess the acute inhalation toxicity potential of Reactive Yellow 217 is available. The calculated value for vapour pressure was found to be 2.7E-37 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. 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 chemical 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 88.3 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 and dermal toxicity studies (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. Hence, the conduct of acute inhalation dose toxicity study for Reactive Yellow 217 is considered to be scientifically not necessary.

Justification for classification or non-classification

Acute oral toxicity:

Based on the above stated assessment of the acute oral toxicity of FAT 40851/A (absence of toxicity up to 2000 mg/kg) the substance does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

 

Acute dermal toxicity:

Based on the above stated assessment of the acute dermal toxicity of FAT 40851/A (absence of toxicity up to 2000 mg/kg) the substance does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

 

Acute inhalation toxicity:

Due to the very low vapour pressure of the FAT 40851/A, the fact that the substance is imported into the EU in a formulated form as a dust-free powder or as a granulate, the inhalation route of exposure is considered to be unlikely. Therefore no classification for acute inhalation toxicity is deemed necessary according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.