Trisodium 2-[[6-[(4-amino-6-chloro-1,3,5-triazin-2-yl)methylamino]-1-hydroxy-3-sulphonato-2-naphthyl]azo]naphthalene-1,5-disulphonate

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline available

Principles of method if other than guideline:

The study report contains the limited information on the test conditions because the study has been performed in 1976. However available information is sufficient to conclude on the classification of the substance. Further the test was performed on the vertebrates and use of results from old experimental studies is one of the options to provide information requested by REACH. New experimental studies with vertebrates must only be conducted if there is no adequate existing information.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Weight at study initiation: 110 - 145 g

Route of administration:

oral: unspecified

Vehicle:

not specified

Doses:

7.943, 10.00 and 12.59 g/kg

No. of animals per sex per dose:

10 animals

Control animals:

no

Details on study design:

- Necropsy of survivors performed: yes

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

9 999 mg/kg bw

Based on:

test mat.

95% CL:

> 9 397 - < 10 640

Mortality:

7.943 g/kg: 0 : 1010.00 g/kg: 5 : 1012.59 g/kg: 10 : 10

Gross pathology:

organs stained with the test substance

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance, Reactive Orange 13, is not classified as acute toxic by oral exposure according to conditions listed in Regulation (EC) 1272/2008 (CLP).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

None

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

None

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

None

Species:

rat

Strain:

other: Tif:RAIf(SPF)

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland- Age at study initiation: 7-8 weeks- Weight at study initiation: 160-215 g- Housing: Macrolon cages type 4- Diet (e.g. ad libitum): Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland),- Water (e.g. ad libitum): water ad libitum ENVIRONMENTAL CONDITIONS - Temperature (°C): 22+3° C - Humidity (%): 55±15% - Air changes (per hr): 15 air changes/h - Photoperiod (hrs dark / hrs light): 12 hours light/day

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

None

Doses:

2000, 5000 mg/kg bw.

No. of animals per sex per dose:

5 males and 5 females per dose level

Control animals:

not specified

Details on study design:

None

Statistics:

None

Preliminary study:

None

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed with the dose of 2000 mg/kg bw, however 1 male out of 5 and 3 females out of 5 were found dead on Day 1 with the dose of 5000 mg/kg bw.

Clinical signs:

other: Dyspnoea, exophthalmos, ruffled fur and curved body position were seen, being common symptoms in acute tests. In addition, sedation and diarrhea was observed.

Gross pathology:

None

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of compound FAT 40170/B in rats is greater than 2000 mg/kg bw.

Executive summary:

The acute oral toxicity of FAT 40170 was evaluated in a limit test using rats. 5 males and 5 females were administered a single dose of 2000 and 5000 mg/kg bw orally. After administration of the compound, the animals were observed for 14 days. Deaths and clinical symptoms were recorded. At the end of the observation period, animals were killed by exsanguination under ether anaesthesia and an autopsy performed. No mortality was observed with the dose of 2000 mg/kg bw, however 1 male out of 5 and 3 females out of 5 were found dead on Day 1 with the dose of 5000 mg/kg bw. Dyspnoea, exophthalmos, ruffled fur and curved body position were seen, being common symptoms in acute tests. In addition, sedation and diarrhoea was observed. At autopsy no changes caused by the administration of FAT 40170/B were seen.In conclusion, the acute oral LD50 of FAT 40170 in rats of both sexes observed over a period of 14 days is greater than 2000 mg/kg bw.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

None

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

None

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

None

Species:

rat

Strain:

other: Tif:RAIf(SPF)

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland- Age at study initiation: 7-8 weeks- Weight at study initiation: 174-219 g - Housing: Macrolon cages type 4- Diet (e.g. ad libitum): Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland)- Water (e.g. ad libitum): water ad libitum ENVIRONMENTAL CONDITIONS - Temperature (°C): 22+3° C - Humidity (%): 55+15% - Air changes (per hr): 15 air changes/h - Photoperiod (hrs dark / hrs light): 12 hours light/day

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

None

Doses:

5000 mg/kg bw.

No. of animals per sex per dose:

5 males and 5 females per dose level

Control animals:

not specified

Details on study design:

None

Statistics:

None

Preliminary study:

None

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: Dyspnoea, exophthalmus, ruffled fur and curved body position were seen, being symptoms frequently observed in acute tests. In addition, a transient sedation was noted.

Gross pathology:

None

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of compound FAT 40170/A in rats is greater than 5000 mg/kg bw.

Executive summary:

The acute oral toxicity of FAT 40170 was evaluated in a limit test usingrats. 5 males and 5 females were administered a single dose of 5000 mg/kg bw orally. After administration of the compound, the animals were observed for 14 days. Deaths and clinical symptoms were recorded. At the end of the observation period, animals were killed by exsanguination under ether anaesthesia and an autopsy performed. No mortality was observed. Dyspnoea, exophthalmus, ruffled fur and curved body position were seen, being symptoms frequently observed in acute tests. In addition, a transient sedation was noted. In conclusion, the acute oral LD50 of FAT 40170/A in rats of both sexes observed over a period of 14 days is greater than 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

year 1981

Deviations:

not specified

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: breeding farm Velaz Praha- Females (if applicable) nulliparous and non-pregnant: yes- Age at study initiation: 8 weeks- Weight at study initiation: 177.2 g (male, average), 173.2 (female, average)- Diet (e.g. ad libitum): granulated feed mixture ALTROMIN 1320 12 g/animal/day- Water (e.g. ad libitum): tap waster ad libitum- Acclimation period: 1 week ENVIRONMENTAL CONDITIONS - Temperature: 22 ± 3°C - Humidity: 40 - 60 % - Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

Route of administration:

inhalation: dust

Type of inhalation exposure:

head only

Vehicle:

air

Remark on MMAD/GSD:

Particle size distribution:1 - 4 µm: 76.29 %4 - 10 µm: 17.29 %10 - 20 µm: 5.20 %above 20 µm: 1.21 %

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION - Method of holding animals in test chamber: head only - Source and rate of air: 10 l/min - System of generating particulates/aerosols: Vright Dust Feed Unit MK2, GA 4170, L. Adams ltd., London - Temperature, humidity, pressure in air chamber: temperature 22°C, humidity 55 %, negative pressure 98 Pa TEST ATMOSPHERE - Brief description of analytical method used: Samples of the atmosphere from the inhalation chamber were collected at a rate 4 l/min; 10 liters of air was taken in total. The collected air passed through the filter cartridge and the concentration of the test substance was determined gravimetrically. VEHICLE - Vehicle: air - Concentration of test material in vehicle (if applicable): 4.97 mg/l

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

4.97 mg/l

No. of animals per sex per dose:

5 males / 5 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days - Frequency of observations and weighing: observation 1 and 2 hours after ending of the exposure, then once a day; body weight on day 0, 7 and 14 - Necropsy of survivors performed: yes - Other examinations performed: clinical signs, body weight, organ weights

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

not observed

Clinical signs:

other: During exposure: orange discharge from the nasal cavity, motor disorders of the body, limbs or tail have not been observedPost exposure period:- 0, 60 and 120 min: piloerection, orange discharge from the nasal cavity, regular breathing 110 - 120 per minut

Body weight:

Average body weight: Treated group:- day 0: 177.2 g (M), 173.2 g (F)- day 7: 181.6 g (M), 175.2 g (F)- day 14: 186.8 g (M), 186.8 g (F) Control group:- day 0: 172.7 g (M), 166.7 g (F)- day 7: 173.3 g (M), 198.0 g (F)- day 14: 188.3 g (M), 208.6 g (F)

Gross pathology:

Pathological examination did not reveal any general or focal pathology changes.

Interpretation of results:

GHS criteria not met

Conclusions:

For Reactive Orange 13, a limit test for acute inhalation toxicity was performed. The test was performed according to the OECD TG 403 methodology. The experimental animals (rats) were exposed to inhalation of the test substance powder in air for 4 hours in a “head-only” inhalation chamber. Actual concentrations of the test substance were determined gravimetrically. Prior to exposure, the particle size was measured microscopically; majority size was in the range of 1-4 μm.During the exposure and during the 14-day observation period there was no death of the test animals.Clinical disorders of the health of the test animals may be considered as a consequence of mechanical irritation of the upper respiratory tract.The results of the limit test did not reveal any adverse effect on the health of the experimental animals.

Executive summary:

For Reactive Orange 13, a limit test for acute inhalation toxicity was performed. The test was performed according to the OECD TG 403 methodology. The experimental animals (rats) were exposed to inhalation of the test substance powder in air for 4 hours in a “head-only” inhalation chamber. Actual concentrations of the test substance were determined gravimetrically. Prior to exposure, the particle size was measured microscopically; majority size was in the range of 1-4 μm.

During the exposure and during the 14-day observation period there was no death of the test animals.

Clinical disorders of the health of the test animals may be considered as a consequence of mechanical irritation of the upper respiratory tract.

Pathological examination revealed the penetration of the test substance into the lung tissue in two males. Mild pulmonary congestion probably was caused due to circulation changes in the euthanasia of animals.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 000 mg/m³ air

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:

1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline available

Principles of method if other than guideline:

The study report contains the limited information on the test conditions because the study has been performed in 1991. However available information is sufficient to conclude on the classification of the substance. Further the test was performed on the vertebrates and use of results from old experimental studies is one of the options to provide information requested by REACH. New experimental studies with vertebrates must only be conducted if there is no adequate existing information.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Weight at study initiation: 276 - 294 g

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE - Area of exposure: 4 × 6 cm - Type of wrap if used: gauze, aluminum foil, plaster bandage REMOVAL OF TEST SUBSTANCE - Washing (if done): - Time after start of exposure: TEST MATERIAL - Amount(s) applied (volume or weight with unit): 5 g/kg - For solids, paste formed: yes VEHICLE - Amount(s) applied (volume or weight with unit): 1.5 mL water

Duration of exposure:

24 h

Doses:

5 g/kg

No. of animals per sex per dose:

5 animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days - Necropsy of survivors performed: yes - Other examinations performed: clinical signs, body weight, gross pathology

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

no animal died

Clinical signs:

other: no clinical signs of intoxication

Gross pathology:

no pathomorphological changes were observed

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance, Reactive Orange 13, is not classified as acute toxic by dermal exposure according to conditions listed in Regulation (EC) 1272/2008 (CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Justification for classification or non-classification

No adverse effect found out in oral, dermal or inhalation exposure route. Reactive Orange 13 does not meet the criteria for classification according to Regulation (EC) No. 1272/2008.