N-[2-[(2-bromo-4,6-dinitrophenyl)azo]-5-(diethylamino)phenyl]acetamide

Endpoint summary

Description of key information

The substance shows a low toxicity. The oral LD50 lies above 5000 mg/kh body weight.

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:

weight of evidence

Study period:

July/August 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

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: WINKELMANN, Borchen
- Age at study initiation: 9-14 weeks
- Weight at study initiation: Mean weight - Males; 155-167g, Females; 150-160g
- Fasting period before study: from about 16 hours before till 4 hours after application
- Housing: in fully air-conditioned rooms in macrolon cages (type 3) on soft wood granulate in groups of 5 animals
- Diet (e.g. ad libitum): Altromin R 1324, ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: at least seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 (± 1.5°C)
- Humidity (%): 60 (± 5 %)
- Photoperiod (hrs dark / hrs light): 12 hours daily

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg body weight

Doses:

5000 mg/kg body weight

No. of animals per sex per dose:

5 males
5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends and public holidays only once. During this time the animals were weighed weekly.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the whole study.

Gross pathology:

The animals killed at the end of the observation period showed no macroscopically visible changes.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results obtained in this study the median lethal dose value (LD50) of the substance for the male and female rat is greater than 5000 mg/kg body weight.

Executive summary:

Acute oral toxicity testing of Disperse Violet 93:1 in the rat yielded a median lethal dose (LD50) above 5000 mg/kg body weight in both male and female animals. No lethality occurred after application of 5000 mg/kg body weight. Development of body weight was not impaired. The animals killed at the end of the observation period showed no macroscopically visible changes. Based on the results obtained in this study the median lethal dose value (LD50) of the substance for the male and female rat is greater than 5000 mg/kg body weight.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

21. June to 05.July 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

as published under Directive 84/449/EWG

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain Bor: WISW (SPF Cpb)
- Source: WINKELMANN, Borchen
- Age at study initiation: 8-10 weeks
- Weight at study initiation: Mean weight - Males; 170g (189-199g), Females; 170g (169-190g)
- Fasting period before study: from about 16 hours before
- Housing: in fully air-conditioned rooms in macrolon cages (type 3) on soft wood granulate in groups of 5 animals
- Diet (e.g. ad libitum): Altromin® 1324 Pellets), ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 (± 2°C)
- Humidity (%): 50 (± 10 %)
- Photoperiod (hrs dark / hrs light): 12 hours daily

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg body weight

Doses:

5000 mg/kg body weight

No. of animals per sex per dose:

5 males
5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends and public holidays only once. During this time the animals were weighed weekly.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the whole study.

Clinical signs:

other: Development of body weight was not impaired.

Gross pathology:

The animals killed at the end of the observation period showed no macroscopically visible changes.

Other findings:

No data

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results obtained in this study the median lethal dose value (LD50) of the substance for the male and female rat is greater than 5000 mg/kg body weight.

Executive summary:

Acute oral toxicity testing of Disperse Violet 93:1 in the rat yielded a median lethal dose (LD50) above 5000 mg/kg body weight in both male and female animals. No lethality occurred after application of 5000 mg/kg body weight. Development of body weight was not impaired. The animals killed at the end of the observation period showed no macroscopically visible changes. Based on the results obtained in this study the median lethal dose value (LD50) of the substance for the male and female rat is greater than 5000 mg/kg body weight.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1977/1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Alderley Park specific pathogen free (SPF) albino rats (Supplied by the Animal Breeding Unit, Imperial Chemical Industries PLC, Pharmaceuticals Division, Macclesfield, Cheshire)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Alderley Park, specific pathogen free (SPF) albino rats
- Weight at study initiation: 150-175 g
- Females (if applicable) nulliparous and non-pregnant
- Housing: group
Justification for the choice: the rat is the preferred rodent species for this study

ENVIRONMENTAL CONDITIONS
- Humidity (%): relative humidity 50-60
- Air changes (per hr): 10-20
- Temperature (°C): RT 19-23 °C
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25%
- Amount of vehicle (if gavage): 2x10 ml/kg bw
- Justification for choice of vehicle: not water souble

Doses:

5000 mg/kg bw.

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: observations fequently on first day thereafter daily; weighing: Day 0, 2, 5, 7, 14
- Necropsy of survivors performed: yes

Statistics:

The acute oral LD50 was estimated from the mortality data.

Preliminary study:

1 male + 1 female at 5000 mg/kg bw with 14 day observation period - without effect

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No

Clinical signs:

other: discoloured urine and faeces

Gross pathology:

no effects

Other findings:

No signs of toxicity were observed in any animal during the study period.

No signs of toxicity were observed in any animal during the study period.

Therefore, Disperce Violet 93:1 (Br) has an LD50 to male and female rats in excess of 5000 mg/kg.

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study, Disperse Violet 93:1 was given orally by gavage at a dose level of 5000 mg/kg bw to 3 male and 3 female rats. No adverse effects were seen, no rats died. The test substance has hence an oral LD50 of more the 5000 mg/kg bw in male and female rats.

Executive summary:

In an acute oral toxicity study, Disperse Violet 93:1 (Br) was given at a single dose level of 5000 mg/kg bw to 3 male and 3 female rats.

On the day of dosing the animals were observed for signs of systemic toxicity once between 30 and 90 minutes and again between 4 and 5 hours after dosing. Subsequent observations were made once daily up to Day 15.

No deaths or signs of toxicity were noted throughout the study period. Body weight development was regular. Hence, Disperse Violet 93:1 (Br) has an oral LD50 of more than 5000 mg/kg bw in male and 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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read across is based on the same physico-chemical properties, a close structural similarity and the same mechanism of action during use processes.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
- Source: Disperse Blue 79:1
Substance Name: 2,2’-[[5-acetamido-4-[(2-bromo-4,6-dinitrophenyl)azo]-2-methoxyphenyl]imino]diethyl diacetate
EC Number: 222-813-1
CAS Number: 3618-72-2

- Target: Disperse Violer 93:1
Substance Name: N-[2-[(2-bromo-4,6-dinitrophenyl)azo]-5-(diethylamino)phenyl]acetamide
EC Number: 258-110-1
CAS Number: 52697-38-8

3. ANALOGUE APPROACH JUSTIFICATION
see attachment section 13

4. DATA MATRIX
see attachment section 13

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

The test was conducted according to an internal procedure.

GLP compliance:

no

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Route of administration:

inhalation: dust

Type of inhalation exposure:

not specified

Vehicle:

air

Remarks:

saturated with test item

Details on inhalation exposure:

Inhalation by means of inhalation of test substance saturated atmosphere for 8 h. To achieve saturation, air was fed through an approx. 5 cm deep layer of the test substance.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

8 h

Concentrations:

saturation concentration

No. of animals per sex per dose:

12 rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations: daily observation
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, necropsy

Statistics:

NA

Preliminary study:

NA

Key result

Sex:

not specified

Dose descriptor:

LC0

Based on:

test mat.

Remarks:

40% purity

Exp. duration:

8 h

Remarks on result:

other: no effect at saturation concentration

Mortality:

no deaths

Clinical signs:

other: no effects

Body weight:

no data

Gross pathology:

no effects

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, no mortality was observed in the treated rats.

Executive summary:

A study was conducted to determine the acute inhalation toxicity of the test substance according to an internal procedure. A group of 12 rats were exposed for 8 h to the vapour of saturated test substance and thereby observed for 14 d. Under the study conditions, no mortality was observed in the treated rats (Munk, 1977).

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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read across is based on the same physico-chemical properties, a close structural similarity and the same mechanism of action during use processes.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
- Source: Disperse Blue 79:1
Substance Name: 2,2’-[[5-acetamido-4-[(2-bromo-4,6-dinitrophenyl)azo]-2-methoxyphenyl]imino]diethyl diacetate
EC Number: 222-813-1
CAS Number: 3618-72-2

- Target: Disperse Violer 93:1
Substance Name: N-[2-[(2-bromo-4,6-dinitrophenyl)azo]-5-(diethylamino)phenyl]acetamide
EC Number: 258-110-1
CAS Number: 52697-38-8

3. ANALOGUE APPROACH JUSTIFICATION
see attachment section 13

4. DATA MATRIX
see attachment section 13

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: CFY

Sex:

male

Details on test animals or test system and environmental conditions:

Weight range: 244 to 264 g

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 10% of the total body surface
- Type of wrap if used: aluminium foil

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm (40-50°C) dilute soap solution, rinsing in clean warm water
- Time after start of exposure: 24 h

Duration of exposure:

24 hours

Doses:

5 mL/kg bw

No. of animals per sex per dose:

10 male rats

Control animals:

yes

Remarks:

treated with water

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations: clinical signs daily; body weight weekly
- Necropsy of survivors performed: yes

Statistics:

NA

Preliminary study:

NA

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 mL/kg bw

Mortality:

no deaths

Clinical signs:

other: slight lethargy and piloerection

Gross pathology:

congestion of the lungs ond pale or uneven col.ouration of the liver and kidneys. Five rats had haemorrhage of.the subcutaneous blood vessels of the treated areas.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, acute dermal LD50 of the test substance in rats was determined to be greater than 5 mL/kg bw.

Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance according to a method equivalent to OECD Guideline 402. No mortality was observed in the treated rats. According to the study conditions, the acute dermal LD50 of the test substance was determined to be greater than 5 mL/kg bw (Davies, 1974).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

In three separate studies, the acute oral toxicity of Disperse Violet 93:1 in the rat was tested at a dose level of 5000 mg/kg body weight in 3 or 5 male and 3 or 5 female rats according to or equivalent to OECD Test Guideline 401. No lethality occurred after application of 5000 mg/kg body weight. Development of body weight was not impaired. The animals killed at the end of the observation period showed no macroscopically visible changes. Based on the results obtained in this study the median lethal dose value (LD50) of the substance for the male and female rat is greater than 5000 mg/kg body weight.

A study was conducted to determine the acute inhalation toxicity of the test substance (Structural Analogue 03) according to an internal procedure. A group of 12 rats were exposed for 8 h to the vapour of saturated test substance and thereafter observed for 14 days. Under the study conditions, no mortality was observed in the treated rats.

A study was conducted to determine the acute dermal toxicity of the test substance according (Structural Analogue 03) to a method equivalent to OECD Guideline 402. No mortality was observed in the treated rats. According to the study conditions, the acute dermal LD50 of the test substance was determined to be greater than 5 mL/kg bw.