Alkali salt of sulfonated aryl azo amino sulfonyl aryl azo sulfonyl aryl azo aryl sulfonate

Endpoint summary

Description of key information

The test item did not induce toxic effects in the rat following oral, dermal or respiratory administration of a single dose at a level of 2000 mg/kg bw or 5000 mg/m³ air, respectively..

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:

08 July 2014 to 01 August 2014

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

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Rat, Hsd: Sprague Dawley SD from Harlan Italy s.r.l., san Pietro al Natisone (UD), Italy; females nulliparous and non-pregnant
- Age at study initiation: 7-8 weeks at allocation
- Weight at study initiation: 177. 1-211.0 g at allocation
- Fasting period before study: yes, approximately 17 hours prior to dosing
- Housing: 3 animals/cage
- Diet (e.g. ad libitum): ad libitum, except for the fasting period prior to dosing
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C+/-2°C
- Humidity (%): 55% +/- 15%
- Air changes (per hr): approximately 15 to 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 08 July 2014 to 01 August 2014

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg body weight
- Justification for choice of vehicle: solubility of the test item

DOSAGE PREPARATION (if unusual): the test item was suspended in the vehicle at concentration of 200 mg/mL

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on the day of dosing, animals were observed for clinical signs on dosing, approximately 0.5, 2 and 4 hours after dosing; daily thereafter for a total of 14 days. All animals were weighed at allocation to the study (Day -1), on the day of dosing (Day 1) and on Days 2, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic observation during the necropsy procedure

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical signs were observed in the first group of animals initially dosed at 2000 mg/kg (Step 1) and in the further group of 3 females dosed at the same dose level (Step 2).

Gross pathology:

No abnormalities were observed at necropsy examination performed on all animals dosed at 2000 mg/kg at the end of the observation period.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

These results indicate that the test item, Reactive Brown DYHY 0331/0334, did not induce toxic effects in the rat following oral administration of a single dose at a level of 2000 mg/kg. The lack of mortality demonstrates the acute toxicity expected (ATE) to be greater than 2000 mg/kg body weight.

European Directives concerning the classification, packaging and labelling of dangerous substances (Council Regulation (EC) No. 1272/2008 and subsequent revisions) would indicate the following:
These results indicate that the test item, Reactive Brown DYHY 0331/0334, did not induce toxic effects in the rat following oral administration of a single dose at a level of 2000 mg/kg. The lack of mortality demonstrates the acute toxicity expected (ATE) to be greater than 2000 mg/kg body weight.

European Directives concerning the classification, packaging and labelling of dangerous substances (Council Regulation (EC) No. 1272/2008 and subsequent revisions) would indicate the following:


These results indicate that the test item, Reactive Brown DYHY 0331/0334, did not induce toxic effects in the rat following oral administration of a single dose at a level of 2000 mg/kg. The lack of mortality demonstrates the acute toxicity expected (ATE) to be greater than 2000 mg/kg body weight.
European Directives concerning the classification, packaging and labelling of dangerous substances (Council Regulation (EC) No. 1272/2008 and subsequent revisions) would indicate the following:
Classification: Not required
Signal word: None indicated
Hazard statement: None indicated

Executive summary:

The acute toxicity of Reactive Brown DYHY 0331/0334 was investigated following a single oral administration to the Sprague Dawley rat followed by a 14-day observation period.

A first group of 3 female animals was initially dosed at 2000 mg/kg bw (Step 1). No mortality occurred and no clinical signs were observed.

A second group of 3 female animals was then dosed at the same dose level (Step 2). No death occurred and no clinical signs were noted.

Body weight changes recorded during the study were within the expected range for this strain and age of animals.

No abnormalities were observed at necropsy examination performed at the end of the observation period on animals of both groups.

These results indicate that the test item, Reactive Brown DYHY 0331/0334, did not induce toxic effects in the rat following oral administration of a single dose at a level of 2000 mg/kg bw. The lack of mortality demonstrates the acute toxicity expected (ATE) to be greater than 2000 mg/kg body weight. The LD50 is higher than 2000 mg/kg bw in female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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:

2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Version / remarks:

2009

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Beijing Vital River Laboratory Animal Technology Co., Ltd.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 54 to 60 days
- Weight at study initiation: 185 to 233 g for male rats and 165 to 173 g for female rats
- Fasting period before study: NA
- Housing: One or two animals were housed per cage during the acclimatization period. Animals were housed individually after exposure
- Diet (ad libitum): rodent complete nutrition pellet diet supplied by Beijing keaoxieli Feed CO., LTD. (Batch numbers: 18053211; 18073231)
- Water (ad libitum): purified tap water using the HT-R01000 purity system
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.1°C to 24.6°C (Target value: 19°C to 25°C)
- Humidity (%): 46% to 75% (Target value: 40% to 70%)
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: July 31, 2018 to August 14, 2018

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Mass median aerodynamic diameter (MMAD):

>= 1 - <= 4 µm

Geometric standard deviation (GSD):

>= 1.5 - <= 3

Details on inhalation exposure:

Equipment: HOPE-MED 8052H dynamic snout only dust inhalation instrument was used.
Exposure Method
Before exposure, each rat was restrained in a confined transparent polyacrylic tube. The exposure tubes were installed in the portholes of the inhalation chamber and the chamber was sealed up. Filtered and compressed air was mixed quantitatively with test item and the aerosol was sent to the exposure chamber (0.04 m³). The test item moving speed and exposure airflow rate had been adjusted to provide the selected target concentration. The aerosol was continuously generated by the generation system on the top of the chamber with an aerosol producer. A slight negative pressure was maintained in the outer plenum of the chamber to prevent leakage of the test substance into the surrounding area. The exhausted air was removed from the outlet at the bottom of the chamber and led to the absorption unit.

The actual concentrations, particle size distribution at the animals’ breathing zone, chamber airflow, chamber temperature, relative humidity and oxygen concentration were determined during the exposure period.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Designed dose (mg/m³): 5000
Actual concentration (mg/m³): 5030

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations were recorded once during the exposure and twice (with about one hour interval) after exposure on the exposure day and then once daily for up to the end of the observation period.
Mortality inspections were made twice daily, morning and afternoon, during normal working days and once daily at weekends and public holidays.
The animals were weighed within the first 24 hours after arrival, on the day of exposure prior to exposure (day 0), and on day 1, day 3, day 7 and day 14.
- Necropsy of survivors performed: yes

Statistics:

The mean and standard deviation of body weight and body weight gains at different times were calculated.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 000 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

none

Clinical signs:

other: none

Body weight:

no effects

Gross pathology:

no effects

Other findings:

Actual Concentration
Actual mean concentration in the cabinet for four times measurement was 5030±58 mg/m³.
Nominal concentration in the cabinet was 53827 mg/m³.

Exposure Chamber Parameters
The air flow rate was 1.08 m³/h.
Temperature, humidity, oxygen and carbon dioxide concentration all met the acceptance criteria.

Particle Size Distribution
The mass median aerodynamic diameters (MMAD) for two measurements were 1.88 μm and 2.04 μm.
The geometric standard deviations (GSD) were 2.29 and 2.35, respectively.
The aerodynamic particle sizes less than 4 micron (mass %) for two measurements were 99.75% and 99.74%, respectively.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results, the acute inhalation LC50 in SD rats for Reactive Brown DYHY 0331/0334 is higher than 5030±58 mg/m³ and it is classified as “unclassified” according to GHS classification.

Executive summary:

The study was designed to assess the acute inhalation toxicity of Reactive Brown DYHY 0331/0334 after being snout only administrated to SD rats for 4 hours and to make GHS classification.

The method was designed to meet the OECD Guideline for the testing of chemicals: Acute Inhalation Toxicity – Acute Toxic Class Method (No.436, 07 September 2009). 6 animals (3 males and 3 females) were exposed for 4 hours using a snout-only exposure system to 5030 mg/m³ ^{test item}. Clinical observations were made once during exposure and twice after exposure on the dosing day and then once daily in 14 days observation period. Body weights were weighed on day 0, day 1, day 3, day 7 and day 14. Concentrations were analysed four times and particle size distributions were measured two times during exposure. Gross necropsy was made to all animals at the end of observation.

No animals were found dead during test period and the mortality was zero. No abnormalities were found during the whole observation period. The body weight development of male and female animals during the observation period was regular. No abnormalities were found in female and male animals at the gross necropsy.

Actual mean concentration in the cabinet resulting from the four times measurement was 5030±58 mg/m³. The mass median aerodynamic diameters (MMAD) from the two measurements were 1.88 μm and 2.04 μm. The geometric standard deviations (GSD) were 2.29 and 2.35, respectively. The aerodynamic particle sizes less than 4 micron (mass %) for the two measurements were 99.75% and 99.74%, respectively.

 

Based on the results, the acute inhalation LC₅₀ in SD rats for Reactive Brown DYHY 0331/0334 is more than 5030±58 mg/m³ and it is classified as “unclassfied”

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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:

From 14 July 2014 to 29 July 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guidelne study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Italy s.r.l., San Pietro al Natisone (UD), Italy
- Age at study initiation: 8 - 10 weeks (at allocation)
- Weight at study initiation: 275.3 - 285.1 g for males; 225.4 - 261.1 g for females
- Housing: individually caged during the study
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): asd libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C +/-2 °C
- Humidity (%): 55% +/- 15%
- Air changes (per hr): Approximately 15 to 20 air changes per hour
- Photoperiod (hrs dark / hrs light): Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours

IN-LIFE DATES: From: 14 July 2014 (allocation day) To: 29 July 2014 (day of necropsy)

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal surface
- % coverage: 10% of the total body surface
- Type of wrap if used: A patch of surgical gauze covered by a strip of synthetic film was placed over the treated site and the whole assembly held in place by encircling the trunk of the animal with a length of elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): corn oil
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- For solids, paste formed: yes, using 1 mL of sterile water.

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for clinical signs on dosing, approximately 1, 2 and 4 hours after dosing on the day of treatment, daily thereafter. All animals were weighed at allocation to the study (Day -1), on the day of dosing (Day 1) and on Days 8 and 15.
- Necropsy of survivors performed: yes, gross necropsy examination for both external and internal abnormalities, with particular attention to the treatment site.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No signs of toxicity were observed in male or female animals after treatment during the observation period. Black staining on the dorsal region, due to the colour of the test item, was observed from Day 2 up to Day 14 of the observation period in the majo

Gross pathology:

No abnormalities were found at necropsy examination performed on all animals at termination of the study.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

These results indicate that the test item, Reactive Brown DYHY 0331/0334, has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg body weight. The lack of mortality demonstrates the acute toxicity expected (ATE) to be greater than 2000 mg/kg.

Executive summary:

The acute toxicity of Reactive Brown DYHY 0331/0334 was investigated following dermal administration of a single dose to the rat.

A single dose of 2000 mg/kg bw was administered to a group of 5 male and 5 female animals for 24 hours. After 14 days, all animals were killed and subjected to necropsy examination.

No mortality occurred and no signs of toxicological relevance were observed in male or female animals during the observation period.

With the exception of a slight decrease seen in a single female, body weights and body weight changes observed during the study were within the expected range for this species and age of animals.

No abnormalities were found at necropsy in the animals at termination of the study.

These results indicate that the test item, Reactive Brown DYHY 0331/0334, has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg bw. The lack of mortality demonstrates the acute toxicity expected (ATE) to be greater than 2000 mg/kg. The dermal LD50 lies above 2000 mg/kg bw for male and female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

The acute toxicity of Reactive Brown DYHY 0331/0334 was investigated following a single oral administration to the Sprague Dawley rat followed by a 14-day observation period.

A first group of 3 female animals was initially dosed at 2000 mg/kg bw (Step 1). No mortality occurred and no clinical signs were observed. Consequently, a second group of 3 female animals was then dosed at the same dose level (Step 2). Again, no death occurred and no clinical signs were noted.

Body weight changes recorded during the study were within the expected range for this strain and age of animals.

No abnormalities were observed at necropsy examination performed at the end of the observation period on all animals.

These results indicate that the test item, Reactive Brown DYHY 0331/0334, did not induce toxic effects in the rat following oral administration of a single dose at a level of 2000 mg/kg bw. The lack of mortality demonstrates the acute toxicity expected (ATE) to be greater than 2000 mg/kg body weight. The LD₅₀ is higher than 2000 mg/kg bw in female rats.

The acute inhalation toxicity of Reactive Brown DYHY 0331/0334 was investigated following a snout only administration to Sprague-Dawley rats for 4 hours, followed by a 14 -day observation period according to OECD Guideline for the testing of chemicals: Acute Inhalation Toxicity – Acute Toxic Class Method (No. 436, 07 September 2009).

6 animals (3 males and 3 females) were exposed to 5030 mg/m³ test item for 4 hours using a snout-only exposure system. Clinical observations were made once during exposure and twice after exposure on the dosing day and then once daily in 14 days observation period. Body weights were weighed on day 0, day 1, day 3, day 7 and day 14. Concentrations were analysed four times and particle size distributions were measured two times during exposure. Gross necropsy was made to all animals at the end of observation.

No animals were found dead during test period and the mortality was zero. No abnormalities were found during the whole observation period.The body weight development of male and female animals during the observation period was regular.No abnormalities were found in female and male animals at the gross necropsy.

Actual mean concentration in the cabinet resulting from the four times measurement was 5030±58 mg/m³. The mass median aerodynamic diameters (MMAD) from the two measurements were 1.88 μm and 2.04 μm. The geometric standard deviations (GSD) were 2.29 and 2.35, respectively. The aerodynamic particle sizes less than 4 micron (mass %) for the two measurements were 99.75% and 99.74%, respectively.

Based on the results, the acute inhalation LC₅₀ in SD rats for Reactive Brown DYHY 0331/0334 is more than 5030±58 mg/m³ and it is classified as “unclassfied”

The acute toxicity of Reactive Brown DYHY 0331/0334 was investigated following dermal administration of a single dose to the rat.

A single dose of 2000 mg/kg bw was administered to a group of 5 male and 5 female animals for 24 hours. After 14 days, all animals were killed and subjected to necropsy examination.

No mortality occurred and no signs of toxicological relevance were observed in male or female animals during the observation period.

With the exception of a slight decrease seen in a single female, body weights and body weight changes observed during the study were within the expected range for this species and age of animals.

No abnormalities were found at necropsy in the animals at termination of the study.

These results indicate that the test item, Reactive Brown DYHY 0331/0334, has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg bw. The lack of mortality demonstrates the acute toxicity expected (ATE) to be greater than 2000 mg/kg. The dermal LD50 lies above 2000 mg/kg bw for male and female rats.

Testing for acute inhalational toxicity was considered not necessary. The test substance has a very low vapour pressure and is a granular or dedusted product with a median particle size above 100 µm. Hence, the potential for the generation of inhalable forms is low. In addition the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. Oral or dermal exposure is considered to be the more likely route of exposure and has been assessed accordingly.

Justification for classification or non-classification

No classification necessary.