Butanamide, 2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[3-oxo-, N,N'-bis(4-chloro-2,5-dimethoxyphenyl and 2,4-xylyl) derivs.

Endpoint summary

Description of key information

Male and female Wistar rats were subjected to test acute oral toxicity. The test substance was administered by gavage at the limit dose of 5000 mg/kg bw (corresponding to 3550 mg submission substance/kg bw). No animal died under these conditions, resulting in a LD50 > 5000 mg/kg bw (corresponding to > 3550 mg submission substance/kg bw).

The submission substance has not to be classified for acute oral toxicity according to Regulation (EC) No 1272/2008.

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:

key study

Study period:

From 5 JAN 1983 to 19 JAN 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 401)

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

other: sesame oil plus emulsifier

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 12,4 % w/w

MAXIMUM DOSE VOLUME APPLIED: 40 ml/kg bw (two times 20 ml/kg bw within 15 minutes)

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 550 mg/kg bw

Remarks on result:

other: 5000 mg test item/kg bw correspond to 3550 mg submission substance/kg bw, no animals died within the observation period

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP regulation

Conclusions:

Single application of the limit dose of 5000 mg test substance, corresponding to 3550 mg submission substance per kg bw did not cause lethality in male and female Wistar rats during the 14 days observation period, resulting in a LD50 > 5000 mg/kg bw (thus corresponding to > 3550 mg submission substance/kg bw).
The test was performed with a test substance which contains relevant amounts of the submission substance. Therefore the test results are considered adequat to fulfill the endpoint requirements.
The results of this study are in accordance with the findings presented in the key study.

Executive summary:

Male and female Wistar rats were subjected to test acute oral toxicity. The test substance was administered by gavage at the limit dose of 5000 mg/kg bw (corresponding to 3550 mg submission substance/kg bw). No animal died under these conditions, resulting in a LD50 > 5000 mg/kg bw (corresponding to > 3550 mg submission substance/kg bw).

The submission substance has not to be classified for acute oral toxicity according to Regulation (EC) No 1272/2008.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 16 MAR 1977 to 30 MAR 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given: comparable to guidelines

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not applicable

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: WISKf(SPF 71), SPF breeding colony
- Weight at study initiation: mean 94 g
- Fasting period before study: 16 h
- Housing: plastic cages
- Diet: Altromin 1324 (Altromin GmbH, Lage/Lippe, Germany), ad libitum
- Water: tap water, ad libitum

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25% suspension in vehicle

Doses:

15000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 15 000 mg/kg bw

Remarks on result:

other: no animals died within the observation period

Mortality:

- no deaths occured

Clinical signs:

other: - after application the tested animals showed a accelerated respiration and ruffeled fur - after application some animals remained in a crouched posture - faeces was yellow-coloured in all animals

Gross pathology:

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

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: other: CLP regulation

Conclusions:

Single application of 15000 mg test substance per kg bw did not cause lethality in female Wistar-rats during the 14 day observation period, resulting in a LD50 > 15000 mg/kg bw.

Executive summary:

Female Wistar-rats were subjected to test acute oral toxicity. The test substance was administered by gavage at the maximal applicable dose of 15000 mg/kg bw. No animal died during the 14 day observation period, resulting in a LD50 >15000 mg/kg bw.

Classification for acute oral toxicity is not necessary according to Regulation (EC) No 1272/2008.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

From 16 MAR 1977 to 30 MAR 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given: comparable to guidelines

Justification for type of information:

please see read across justification document in chapter 13

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not applicable

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: WISKf(SPF 71), SPF breeding colony
- Weight at study initiation: mean 94 g
- Fasting period before study: 16 h
- Housing: plastic cages
- Diet: Altromin 1324 (Altromin GmbH, Lage/Lippe, Germany), ad libitum
- Water: tap water, ad libitum

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25% suspension in vehicle

Doses:

15000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 15 000 mg/kg bw

Remarks on result:

other: no animals died within the observation period

Mortality:

- no deaths occured

Clinical signs:

other: - after application the tested animals showed a accelerated respiration and ruffeled fur - after application some animals remained in a crouched posture - faeces was yellow-coloured in all animals

Gross pathology:

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

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: other: CLP regulation

Conclusions:

Single application of 15000 mg test substance per kg bw did not cause lethality in female Wistar-rats during the 14 day observation period, resulting in a LD50 > 15000 mg/kg bw.

Executive summary:

Female Wistar-rats were subjected to test acute oral toxicity. The test substance was administered by gavage at the maximal applicable dose of 15000 mg/kg bw. No animal died during the 14 day observation period, resulting in a LD50 >15000 mg/kg bw.

Classification for acute oral toxicity is not necessary according to Regulation (EC) No 1272/2008.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From 14 APR 2004 to 29 APR 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 423)

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: Harlan Winkelmann GmbH, Borchen, Germany
- Age at study initiation: 6 to 10 weeks
- Weight at study initiation: mean 182 g
- Housing: fully air-conditioned rooms in Makrolon cages (Type 4) in groups of 3
- Diet (e.g. ad libitum): ssniff(R) R/M-H, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+-3% (except short lasting deviations due to disturbances of air condition )
- Humidity (%): 50+-20% (except short lasting deviations due to disturbances of air condition )
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 5 % suspension

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw
- Treatment four applications in a 30 minutes interval

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: due to toxicity data of related compounds

Doses:

limit dose: 2000 mg/kg bw

No. of animals per sex per dose:

two times 3 animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: weekly
- Frequency of observations: twice every day/ weekends and holidays only once
- Necropsy of survivors performed: yes

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 230 mg/kg bw

Remarks on result:

other: no animals died within the observation period; 2000 mg/kg bw test item correspond to 1230 mg/kg bw submission substance

Mortality:

-no deaths occured

Clinical signs:

other: - clinical signs were observed starting between 2 and 4 h after the first application of test substance in three animals: stupor, squatting posture, bristled coat and yellow-coloured faeces - in one of these three animals diarrhea occured too after 4 h po

Gross pathology:

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

Conclusions:

Single application of the limit dose of 2000 mg test substance per kg bw did not cause lethality in female Sprague Dawley rats during the 14 days observation period, resulting in a LD50 > 1230 mg submission substance/kg bw.

Executive summary:

Female rats were subjected to test acute oral toxicity according to the acute class method (OECD TG 423). The test substance was administered by gavage at the limit dose of 2000 mg/kg bw. No animal died within the observation period, resulting in a LD50 > 2000 mg/kg bw (corresponding to 1230 mg submission substance/kg bw).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 550 mg/kg bw

Quality of whole database:

reliable

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given: comparable to guidelines

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

: 10 hrs light cycle, some exposure data are missing (e.g. MMAD (not calculated), equilibration period)

GLP compliance:

no

Remarks:

Study pre-dates GLP-regulation

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: in house breeding, SPF breeding colony
- Weight at study initiation: 170 - 190 g
- Housing: in Macrolon cages (type 4) in groups of 10, males and females separated
- Diet: NAFAG (Gossau SG, Switzerland), ad libitum
- Water: ad libitum
- Acclimation period: at least 4 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-1
- Humidity (%): 55+/-5
- Photoperiod: 10 hrs light cycle day

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: inhalation cylinder
- Method of holding animals in test chamber: seperate PVC tubes
- System of generating aerosols: Injecting the solid material with the help of "Grafix Exactometer injector" into an air stream which was discharged into the exposure chamber through a nozzle under a pressure of 2 atm. at a rate of 20 L/min.
- Method of particle size determination: gravimetrically
- Temperature, humidity, oxygen: 24 °C, 38%, 20 Vol.%

TEST ATMOSPHERE
- Brief description of analytical method used: Concentration was determined gravimetrically by sampling the test atmosphere through a selectron filter of 50 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 10 L/min. The size distribution of the particles was measured with a Cascade Impactor with selectron filters of 25 mm diameter and with pore size of 0.2 µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 17.5 L/min.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 1 µm to 7 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not calculated

Analytical verification of test atmosphere concentrations:

yes

Remarks:

: gravimetric measurement

Duration of exposure:

4 h

Concentrations:

4250 (+/-128) mg/m³

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 4 250 mg/m³ air (analytical)

Exp. duration:

4 h

Remarks on result:

other: no animals died within the 14 day observation period

Mortality:

- no death occurred

Clinical signs:

other: - within 3 to 4 hours after starting the exposure period rats showed dyspnoea, curved or ventral position and ruffled fur - recovery within 4 days

Gross pathology:

- no macroscopically visible changes were found

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: other: CLP regulation

Conclusions:

Exposure of male and female rats to 4250 mg/m³ test item for 4 hours did not result in the death of the animals during a 14 day observation period, resulting in a LC50 value of > 4250 mg/m³.

Executive summary:

Acute inhalation toxicity of the test item has been investigated in male and female Tif: RAIf (SPF) rats (10 per sex). They were exposed to 4250 mg test substance per cubic meter for 4 h (maximal applicable dose). All animals survived the 14 day observation period. No macroscopic visible changes were observed at necropsy at the end of the observation period, resulting in a LC50 value of > 4250 mg/m³ (4.25 mg/L) for the inhalation of aerosol.

Classification for acute inhalation toxicity is not necessary according to Regulation (EC) No 1272/2008 .

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

Please see read across justification in Chapter 13

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

LC0

Effect level:

> 4 250 mg/m³ air (analytical)

Based on:

test mat.

Reference 3

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given: comparable to guidelines

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

: 10 hrs light cycle, some exposure data are missing (e.g. MMAD (not calculated), equilibration period)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: in house breeding, SPF breeding colony
- Weight at study initiation: 180 - 210 g
- Housing: in Macrolon cages (type 4) in groups of 10, males and females separated
- Diet: NAFAG (Gossau SG, Switzerland), ad libitum
- Water: ad libitum
- Acclimation period: at least 4 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+-1
- Humidity (%): 55+-5
- Photoperiod: 10 hrs light cycle day

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: inhalation cylinder
- Method of holding animals in test chamber: seperate PVC tubes
- System of generating aerosols: Injecting the solid material with the help of "Grafix Exactometer injector" into an air stream which was discharged into the exposure chamber through a nozzle under a pressure of 2 atm. at a rate of 20 L/min.
- Method of particle size determination: gravimetrically
- Temperature, humidity, oxygen: 25 °C, 38%, 19 Vol.%

TEST ATMOSPHERE
- Brief description of analytical method used: Concentratioin was determined gravimetrically by sampling the test atmosphere through a selectron filter of 50 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 10 L/min. The size distribution of the particles was measured with a Cascade Impactor with selectron filters of 25 mm diameter and with pore size of 0.2 µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 17.5 L/min.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: < 1 µm to > 7 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not calculated

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric measurement

Duration of exposure:

4 h

Concentrations:

2237 +/- 235 and 4448 +/- 407 mg/m³

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4 400 mg/m³ air (analytical)

Exp. duration:

4 h

Remarks on result:

other: no animals died within the 14 day observation period

- no deaths occurred

- within 3 to 4 hours after starting the exposure period the rats in both concentrations showed dyspnoea, exophthalmos, curved or ventral position and ruffled fur, these symptoms were more pronounced at the higher concentration

- recovery within 7 to 9 days

- no substance related gross organ changes were seen

Conclusions:

Exposure of male and female rats to 4400 mg/m³ test item (corresponding to 2508 mg/m³ pigment) for 4 hours did not result in the death of the animals during a 14 day observation period, resulting in a LC50 value of > 4400 mg/m³ (corresponding to a LC50 > 2508 mg/m³ for pigment only).
The test was performed with the test item which contains relevant amounts of the submission substance. Therefore, the test results are considered adequate to fulfil the endpoint requirements. The results of this study are in accordance with the findings presented in the key study.

Executive summary:

Acute inhalation toxicity of the test item has been investigated in male and female Tif: RAIf (SPF) rats (10 per sex and dose). They were exposed to 4400 mg test substance (corresponding to 2508 mg pigment) per cubic meter for 4 h (maximal applicable dose). All animals survived the 14 day observation period. No macroscopic visible changes were observed at necropsy at the end of the observation period, resulting in a LC50 value of > 4400 mg/m³ (corresponding to 2508 mg/m³ pigment) for the inhalation of aerosol.

Reference 4

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

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 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

: 10 hrs light cycle, some exposure data are missing (e.g. MMAD (not calculated), equilibration period)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: in house breeding, SPF breeding colony
- Weight at study initiation: 170 - 190 g
- Housing: in Macrolon cages (type 4) in groups of 10, males and females separated
- Diet: NAFAG (Gossau SG, Switzerland), ad libitum
- Water: ad libitum
- Acclimation period: at least 4 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-1
- Humidity (%): 55+/-5
- Photoperiod: 10 hrs light cycle day

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: inhalation cylinder
- Method of holding animals in test chamber: seperate PVC tubes
- System of generating aerosols: Injecting the solid material with the help of "Grafix Exactometer injector" into an air stream which was discharged into the exposure chamber through a nozzle under a pressure of 2 atm. at a rate of 20 L/min.
- Method of particle size determination: gravimetrically
- Temperature, humidity, oxygen: 24 °C, 38%, 20 Vol.%

TEST ATMOSPHERE
- Brief description of analytical method used: Concentration was determined gravimetrically by sampling the test atmosphere through a selectron filter of 50 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 10 L/min. The size distribution of the particles was measured with a Cascade Impactor with selectron filters of 25 mm diameter and with pore size of 0.2 µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 17.5 L/min.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: < 1 µm to > 7 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not calculated

Analytical verification of test atmosphere concentrations:

yes

Remarks:

: gravimetric measurement

Duration of exposure:

4 h

Concentrations:

4250 (+/-128) mg/m³

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4 250 mg/m³ air (analytical)

Exp. duration:

4 h

Remarks on result:

other: no animals died within the 14 day observation period

Mortality:

- no death occurred

Clinical signs:

other: - within 3 to 4 hours after starting the exposure period rats showed dyspnoea, curved or ventral position and ruffled fur - recovery within 4 days

Gross pathology:

- no macroscopically visible changes were found

Interpretation of results:

GHS criteria not met

Conclusions:

Exposure of male and female rats to 4250 mg/m³ test item for 4 hours did not result in the death of the animals during a 14 day observation period, resulting in a LC50 value of > 4250 mg/m³.

Executive summary:

Acute inhalation toxicity of the test item has been investigated in male and female Tif: RAIf (SPF) rats (10 per sex). They were exposed to 4250 mg test substance per cubic meter for 4 h (maximal applicable dose). All animals survived the 14 day observation period. No macroscopic visible changes were observed at necropsy at the end of the observation period, resulting in a LC50 value of > 4250 mg/m³ (4.25 mg/L) for the inhalation of aerosol.

Classification for acute inhalation toxicity is not necessary according to Regulation (EC) No 1272/2008 .

Reference 5

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:

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

Remarks:

Study performed using analogue substance

Justification for type of information:

See jusitifcation document in Chapter 13

Reason / purpose for cross-reference:

read-across source

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4 250 mg/m³ air (analytical)

Exp. duration:

4 h

Remarks on result:

other: no animals died within the 14 day observation period

Mortality:

- no death occurred

Clinical signs:

other: - within 3 to 4 hours after starting the exposure period rats showed dyspnoea, curved or ventral position and ruffled fur - recovery within 4 days

Gross pathology:

- no macroscopically visible changes were found

Interpretation of results:

GHS criteria not met

Conclusions:

Exposure of male and female rats to 4250 mg/m³ test item for 4 hours did not result in the death of the animals during a 14 day observation period, resulting in a LC50 value of > 4250 mg/m³.

Executive summary:

Acute inhalation toxicity of the test item has been investigated in male and female Tif: RAIf (SPF) rats (10 per sex). They were exposed to 4250 mg test substance per cubic meter for 4 h (maximal applicable dose). All animals survived the 14 day observation period. No macroscopic visible changes were observed at necropsy at the end of the observation period, resulting in a LC50 value of > 4250 mg/m³ (4.25 mg/L) for the inhalation of aerosol.

Classification for acute inhalation toxicity is not necessary according to Regulation (EC) No 1272/2008 .

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

4 250 mg/m³ air

Quality of whole database:

reliable

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1972

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, sufficiently-documented study report, which meets basic scientific principles

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

: no details given on the duration of the exposure; no details given on the occlusion made on the application site; dose tested (1710 mg/kg bw) is lower than the recommended limit dose (2000 mg/kg bw); only 7 days postobservation period

GLP compliance:

no

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: in house breeding
- Age at study initiation: 8 weeks
- Weight at study initiation: males mean: 322 g; females mean: 210 g
- Housing: single caged
- Diet: pelleted diet (Oakes of Congleton), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/-2
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

not specified

Vehicle:

other: 50:50 mixture: polyethylene glycol/water

Details on dermal exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3000 mg/kg bw
- For solids, paste formed: yes (1 g of test item was mixed with 2.5 ml of vehicle)

Duration of exposure:

no data

Doses:

9.9 ml of paste per kg bw (equivalent to 3000 mg test item per kg bw)

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 000 mg/kg bw

Remarks on result:

other: corresponds to 1710 mg/kg bw pure Pigment Yellow 13

Mortality:

- no deaths occurred

Clinical signs:

other: - no clinical symptoms were recorded

Gross pathology:

- No macroscopically visible changes occurred at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP regulation

Conclusions:

The test item was not toxic to male and female Sprague-Dawley rats after dermal application, resulting in a dermal LD50 > 3000 mg/kg bw (corresponding to > 1710 mg PY13/kg bw).
The test was performed with the test item which contains relevant amounts of the submission substance. Therefore, the test results are considered adequate to fulfil the endpoint requirements.

Executive summary:

Acute dermal toxicity of the test item was tested in male and female Sprague-Dawley rats. The maximal applicable dose (3 g test item /kg bw suspended in polyethylene glycol:water 50:50 - final volume 9.9 ml; corresponding to 1710 mg PY13/kg bw) were applied to the skin. No clinical signs were observed and no animals died during the 7 day observation period, resulting in a LD50 > 3000 mg/kg bw (corresponding to > 1710 mg PY13/kg bw).

Classification for acute dermal toxicity is not necessary according to Regulation (EC) No 1272/2008.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

1972

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:

please see read across justification document in chapter 13

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

: no details given on the duration of the exposure; no details given on the occlusion made on the application site; dose tested (1710 mg/kg bw) is lower than the recommended limit dose (2000 mg/kg bw); only 7 days postobservation period

GLP compliance:

no

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: in house breeding
- Age at study initiation: 8 weeks
- Weight at study initiation: males mean: 322 g; females mean: 210 g
- Housing: single caged
- Diet: pelleted diet (Oakes of Congleton), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/-2
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

not specified

Vehicle:

other: 50:50 mixture: polyethylene glycol/water

Details on dermal exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3000 mg/kg bw
- For solids, paste formed: yes (1 g of test item was mixed with 2.5 ml of vehicle)

Duration of exposure:

no data

Doses:

9.9 ml of paste per kg bw (equivalent to 3000 mg test item per kg bw)

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 000 mg/kg bw

Remarks on result:

other: corresponds to 1710 mg/kg bw pure Pigment Yellow 13; no animals died within the observation period

Mortality:

- no deaths occurred

Clinical signs:

other: - no clinical symptoms were recorded

Gross pathology:

- No macroscopically visible changes occurred at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item was not toxic to male and female Sprague-Dawley rats after dermal application, resulting in a dermal LD50 > 3000 mg/kg bw (corresponding to > 1710 mg PY13/kg bw).
The test was performed with the test item which contains relevant amounts of the submission substance. Therefore, the test results are considered adequate to fulfil the endpoint requirements.

Executive summary:

Acute dermal toxicity of the test item was tested in male and female Sprague-Dawley rats. The maximal applicable dose (3 g test item /kg bw suspended in polyethylene glycol:water 50:50 - final volume 9.9 ml; corresponding to 1710 mg PY13/kg bw) were applied to the skin. No clinical signs were observed and no animals died during the 7 day observation period, resulting in a LD50 > 3000 mg/kg bw (corresponding to > 1710 mg PY13/kg bw).

Classification for acute dermal toxicity is not necessary according to Regulation (EC) No 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

1 710 mg/kg bw

Quality of whole database:

reliable

Justification for classification or non-classification

Based on the reported study data Pigment Yellow 176 has not to be classified for acute toxicity.

Furthermore, Pigment Yellow 176 has not to be classified for specific target organ toxicity – single exposure according to Regulation (EC) No 1272/2008, as no specific toxic effects were observed after acute exposure.