trisodium 3-amino-4-[4-[4-(2-(2-ethenylsulfonylethoxy)ethylamino)-6-fluoro-1,3,5-triazine-2-ylamino]-2-sulfophenylazo]-5-hydroxynaphthalene-2,7-disulfonate

Endpoint summary

Description of key information

The oral and dermal LD50 were found to be greater than 2000 mg/kg.

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 - 14 April 1999; Experiment completion date - 07 May 1999; Study completion date - 11 May 1999.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

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:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

Identity: FAT 40574/B
Batch: WP 23/99
Purity: Approx 75 %
Appearance: Solid, dark-red powder
Storage: At room temperature at about 20 °C
Expiration Date: 08 February 2006

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Age when treated: Females: 10 weeks; Males: 8 weeks
Identification: By unique cage number and corresponding color-coded spots on the tail.
Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.
Conditions: Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, with target ranges for room temperature 22 ± 3 °C and relative humidity 40-70 % (values above 70 % during cleaning process possible).
Room environment was monitored continuously with hourly recordings. The room was illuminated by fluorescent light on a 12 hour light/dark cycle. Recorded music was played for approximately 8 hours during the light period.
Accommodation: Groups of three in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz)
Diet: Pelleted standard Kliba 3433, batch no. 35/98, rat maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst) available ad libitum (except for the overnight fasting period prior to intubation).
Water: Community tap water from Itingen, available ad libitum.

Route of administration:

oral: gavage

Vehicle:

other: Bidistilled water

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Mortality / Viability: Four times during test day 1 and once daily during days 2-15.
- Body weights: On test day 1 (pre-administration), 8 and 15.
- Clinical signs: Each animal was examined for changes in appearance and behavior four times during day 1, and once daily during days 2-15.

Statistics:

No statistical analysis was used as no deaths occurred.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Male: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0

Clinical signs:

other: CLINICAL SIGNS: No clinical signs of toxicity were observed.

Gross pathology:

Effects on organs: No treatment-related macroscopic findings were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of FAT 40574/B was found to be greater than 2000 mg/kg.

Executive summary:

The purpose of this study was to assess the acute oral toxicity of FAT 40574/B when administered by single oral gavage to rats, followed by an observation period of 14 days. This study was conducted according to OECD test guideline 423 in a GLP certified laboratory. Two groups, each using three female or three male Hanlbm: WIST (SPF) rats, were treated with FAT 40574/B at 2000 mg/kg by oral gavage. The test article was suspended in vehicle (bi-distilled water) at a concentration of 0.2 g/ml and administered at a volume of 10 ml/kg. The animals were examined for clinical signs four times during test day 1 and once daily during test days 2-15. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically. No death occurred during the study. No clinical signs were observed during the observation period. The body weight of the animals was within the range commonly recorded for animals of this strain and age. No macroscopic findings were observed at necropsy. Based on the findings of this study, the LD50 of FAT 40574/B was found to be greater than 2000 mg/kg.

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

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 - 20 May 1999; Experiment end date - 10 June 1999; Study completion date - 22 June 1999.

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))

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:

Identity: FAT 40574/B
Batch: WP 23/99
Purity: Approx. 75 %
Appearance: Solid, dark-red powder
Storage: At room temperature at about 20 °C
Expiration Date: 08 February 2006

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Age when treated: Females: 11 weeks; Males: 9 weeks
Identification: By unique cage number and corresponding color-coded spots on the tail.
Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.
Conditions: Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, with target ranges for room temperature 22 ± 3 °C and relative humidity 40-70 % (values above 70% during cleaning process possible). Room environment was monitored continuously with hourly recordings. The room was illuminated by fluorescent light on a 12 hour light/dark cycle. Recorded music was played for approximately 8 hours during the light period.
Accommodation: Groups of three in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz)
Diet: Pelleted standard Kliba 3433, batch no. 35/98, rat maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst) available ad libitum (except for the overnight fasting period prior to intubation).
Water: Community tap water from Itingen, available ad libitum.

Type of coverage:

semiocclusive

Vehicle:

other: Bidistilled water

Details on dermal exposure:

Approximately 24 hours before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10 % of the total body surface. Only those animals without injury or irritation on the skin were used in the test. On test day 1, the test article was applied at a dose of 2000 mg/kg body weight evenly on the intact 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. Application volume/kg body weight: 6.0 ml
Twenty-four hours after the application the dressing was removed and the skin was flushed with lukewarm tap water and dried with disposable paper towels. Thereafter, the reaction sites were assessed.

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not required

Details on study design:

Mortality / Viability: Four times during test day 1 and once daily during days 2-15.
Body weights: On test day 1 (pre-administration), 8 and 15.
Clinical signs: Each animal was examined for changes in appearance and behavior four times during day 1, and once daily during days 2-15. A description of all abnormalities was recorded.
Necropsies were performed by experienced prosectors. At the end of the observation period all animals were sacrificed by intraperitoneal injection of NARCOREN (Rhône Merieux GmbH, D-88471 Laupheim) at a dose of at least 2.0 ml/kg body weight (equivalent to at least 320 mg
sodium pentobarbitone/kg body weight). The animals were examined macroscopically and all abnormalities recorded. Thereafter, they were discarded.

Statistics:

No statistical analysis was used as no deaths occurred.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: CLINICAL SIGNS: No clinical signs of toxicity were observed. BODY WEIGHTS: No changes on body weights noted.

Gross pathology:

Effects on organs:
No treatment-related macroscopic findings were observed.

Other findings:

Signs of toxicity (local):
Test article remnants were observed in one animal between day 2 and day 13 and in two animals between day 2 until the end of the observation period. Slight scaling was noted until day 6 (two animals) and 7 (one animal).

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 of FAT 40574/B was found to be greater than 2000 mg/kg body weight

Executive summary:

The purpose of this study was to assess the acute dermal toxicity of FAT 40574/B when administered to rats by a single semi-occlusive dermal application, followed by an observation period of 14 days. This study was conducted according to OECD test guideline 402 in a GLP-certified laboratory. A group of five male and five female Hanlbm: WIST (SPF) rats was treated with FAT 40574/B at 2000 mg/kg by dermal application. The test article was suspended in vehicle (bidistilled water) at a concentration of 0.33 g/ml and administered at a volume of 6 ml/kg. The animals were examined for clinical signs four times during day 1 and once daily during days 2-15. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically. No deaths occurred during the study. In all animals, test article remnants were observed on test day 2 and persisted in two animals until test day 13 and in the other animals until the end of the observation period. In three males, slight to moderate scaling was noted until test day 6 (two animals) and 7 (one animal). The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy. The median lethal dose of FAT 40'574/B after single dermal administration to rats of both sexes, observed over a period of 14 days, could not be estimated as no death occurred. LD50: greater than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity

The purpose of this study was to assess the acute oral toxicity of FAT 40574/B when administered by single oral gavage to rats, followed by an observation period of 14 days. This study was conducted according to OECD test guideline 423 in a GLP certified laboratory. Two groups, each using three female or three male Hanlbm: WIST (SPF) rats, were treated with FAT 40'574/B at 2000 mg/kg by oral gavage. The test article was suspended in vehicle (bi-distilled water) at a concentration of 0.2 g/ml and administered at a volume of 10 ml/kg. The animals were examined for clinical signs four times during test day 1 and once daily during test days 2-15. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically. No death occurred during the study. No clinical signs were observed during the observation period. The body weight of the animals was within the range commonly recorded for animals of this strain and age. No macroscopic findings were observed at necropsy. Based on the findings of this study, the LD50 of FAT 40574/B was found to be greater than 2000 mg/kg.

Acute inhalation waiver

Currently no study to assess the acute inhalation toxicity potential of Reactive Red 271 is available. The calculated value for vapour pressure was found to be 9.95E-22 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 >170 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 the above arguments into consideration, low toxicity potential is expected on acute exposure of Reactive Red 271 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.

Acute dermal toxicity

The purpose of this study was to assess the acute dermal toxicity of FAT 40574/B when administered to rats by a single semi-occlusive dermal application, followed by an observation period of 14 days. This study was conducted according to OECD test guideline 402 in a GLP-certified laboratory. A group of five male and five female Hanlbm: WIST (SPF) rats was treated with FAT 40'574/B at 2000 mg/kg by dermal application. The test article was suspended in vehicle (bidistilled water) at a concentration of 0.33 g/ml and administered at a volume of 6 ml/kg. The animals were examined for clinical signs four times during day 1 and once daily during days 2-15. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically. No deaths occurred during the study. In all animals, test article remnants were observed on test day 2 and persisted in two animals until test day 13 and in the other animals until the end of the observation period. In three males, slight to moderate scaling was noted until test day 6 (two animals) and 7 (one animal). The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy. The median lethal dose of FAT 40574/B after single dermal administration to rats of both sexes, observed over a period of 14 days, could not be estimated as no death occurred. LD50 : greater than 2000 mg/kg body weight.

Justification for classification or non-classification

The oral and dermal LD50s were found to be greater than 2000 mg/kg. Also, no deaths and no clinical signs were noted in these studies. Hence, Reactive Red 271 is not required to be classified for acute toxicity or specific target organ toxicity on single exposure in accordance with CLP (Regulation EC No. 1272/2008).