2,9-dichloro-5,12-dihydroquino[2,3-b]acridine-7,14-dione

Endpoint summary

Description of key information

Oral:

LD50 (Pigment Red 202, not specific form) >5000 mg/kg

LD50 (strucrue analogue Pigment Violet 19, nano form) >10000 mg/kg

LD50 (strucrue analogue Pigment Red 122, nano form) >2000 mg/kg

Inhalation:

LC0 (strucrue analogue Pigment Red 122, nano form) 3.055 mg/L (highest technicallly achivable concentration)

 

Dermal: waiving

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:

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

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Please refer to attached read across justification document (Chapter 13).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to attached read across document (Chapter 13).

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to attached read across justification document (Chapter 13).

4. DATA MATRIX
Please refer to attached read across justification document (Chapter 13).

Reason / purpose for cross-reference:

read-across source

Sex:

female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Remarks on result:

other: no animals died within the 14 days observation period

Mortality:

- no deaths occured

Clinical signs:

other: - dye was excreted in the faeces - no other clinical signs observed

Gross pathology:

- in the animals sacrificed at the end of the observation period no macroscopically visible changes were found

Interpretation of results:

GHS criteria not met

Remarks:

CLP Regulation

Conclusions:

The toxicity profile of Pigment Red 202 is assessed based on analogue approaches: Single application of the limit dose of 10000 mg test item per kg bw did not cause lethality in female rats during the 14 days observation period, resulting in a LD50 > 10000 mg/kg bw.

Executive summary:

Female Wistar rats were subjected to test acute oral toxicity. The test item was administered at the limit dose of 10000 mg/kg bw to ten rats. During the 14 days observation period no animals died and there were no changes found in necropsy, thus leading to a median lethal dose (LD50) > 10000 mg/kg bw.

Therefore, the test item 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:

22 June 2005 to 11 August 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Study in compliance with Swiss Ordinance relating to GLP, which is based on OECD Principles of GLP

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain specifics: HanRcc:WIST (SPF)
- Source: RCC Ltd, Laboratory Animal services, Füllinsdorf, Switzerland
- Age at study initiation: 11-13 weeks
- Weight at study initiation: 173.8-192.2 g on day 1 (treatment)
- Fasting period before study: approximately 18 hours before treatment, access to water permitted)
- Housing: in groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): standard rat/mouse maintenance diet, ad libitum
- Water (e.g. ad libitum): community tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/ml
- Amount of vehicle (if gavage): 10 ml/kg body weight (volume of test item in vehicle)
- Justification for choice of vehicle: solubility trial before the study initiation date (excluded from GLP statement of compliance)
- Vehicle Lot/batch no. (if required): 1107712 24104041

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days starting with treatment day 1
- Frequency of observations and weighing:
mortality/viability: during the first 30 minutes and approximately 1, 2, 3 and 5 h after administration on day 1 and twice daily on days 2-15
clinical signs: during the first 30 minutes and approximately 1, 2, 3 and 5 h after administration on day 1 and daily on days 2-15
body weights: on days 1 (prior to administration), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination

Statistics:

None

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No deaths

Clinical signs:

other: Red faeces in all animals from test day 2 to 5 (3 animals) or 6 (3 animals), slightly ruffled fur in 3/6 animals from 30 minutes until 2, 3 or 5 hours (different duration in each of the affected animals) after treatment on day 1.

Gross pathology:

Congestion of the lungs in one animal, but no macroscopic findings in the remaining five animals at scheduled necropsy.

Interpretation of results:

GHS criteria not met

Remarks:

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

Conclusions:

The median lethal dose (LD50) of test item (Pigment Red 122) after a single oral administration to female rats, observed over a period of 14 days, was greater than 2000 mg/kg body weight.

Executive summary:

Two groups, each of three female HanRcc:WIST (SPF) rats, were treated with the test item (Pigment Red 122) by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at a concentration of 0.2 g/mL and administered at a volume dosage of 10 mL/kg.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality / viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period.

Red feces were observed in all animals from test day 2 to 5 or test day 6. Three out of 6 animals were noted with slightly ruffled fur from the observation performed within the first 30 minutes after application to the 2-, 3- or 5 -hour reading.

The body weight of the animals was within the range commonly recorded for this strain and age.

Congestion of the lungs was noted in one animal whereas no macroscopic findings were recorded in the remaining five animals at scheduled necropsy.

The median lethal dose of the test item after single oral administration to female rats, observed over a period of 14 days is:

LD50 (female rat): greater than 2000 mg/kg body weight

Therefore, the test item has not to be classified as acutely toxic by the oral route according to Regulation (EC) No 1272/2008.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 5 APR 1979 to 19 APR 1979

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:

yes

Remarks:

: no individual data included in report

GLP compliance:

no

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: in-house breeding (Hoe WISKf (SPF71))
- Weight at study initiation: 160 to 176 g
- Fasting period before study: 16 hours
- Housing: in plastic cages in groups
- Diet: Altromin 1324 (Altromin GmbH, Lage/lippe, Germany), ad libitum
- Water: tap water, ad libitum

Route of administration:

oral: gavage

Vehicle:

other: starch mucilage (2%)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 12.5% suspension in 2% starch mucilage

Doses:

10000 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
- Other examinations performed: clinical signs

Sex:

female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Remarks on result:

other: no animals died within the 14 days observation period

Mortality:

- no deaths occured

Clinical signs:

other: - dye was excreted in the faeces - no other clinical signs observed

Gross pathology:

- in the animals sacrificed at the end of the observation period no macroscopically visible changes were found

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 10000 mg test item per kg bw did not cause lethality in female rats during the 14 days observation period, resulting in a LD50 > 10000 mg/kg bw.

Executive summary:

Female Wistar rats were subjected to test acute oral toxicity. The test item was administered at the limit dose of 10000 mg/kg bw to ten rats. During the 14 days observation period no animals died and there were no changes found in necropsy, thus leading to a median lethal dose (LD50) > 10000 mg/kg bw.

Therefore, the test item has not to be classified for acute oral toxicity according to Regulation (EC) No 1272/2008.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 31 AUG 1982 to 23 SEP 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

: limit dose of 11000 mg/kg bw exceeds required dose, no data of single animals are reported, no necropsy performed

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Crl:CD

Sex:

male

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 32 %

AVERAGE DOSE VOLUME APPLIED: 9.01 mL

Doses:

11000 mg/kg bw (divided in 2 portions 15 minutes apart)

No. of animals per sex per dose:

10

Control animals:

no

Sex:

male

Dose descriptor:

LD50

Effect level:

> 11 000 mg/kg bw

Remarks on result:

other: no animals died within the 14 days observation period

- no deaths occurred

- compound stained body

- compound and/or metabolites in faeces

- diarrhea

- wet perineal area

- body weight loss (average body weight: 262 g)

Conclusions:

Application of 11000 mg test item per kg bw did not cause lethality in male rats during the 14 day observation period, resulting in a LD50 > 11000 mg/kg bw.
The results of this study are in accordance with the findings presented in the key study.

Executive summary:

Male Crl:CD rats were subjected to test acute oral toxicity. The test substance was administered by gavage at the limit dose of 11000 mg/kg bw to ten rats. During the 14 days observation period no animals died under these conditions, thus leading to a LD50 > 11000 mg/kg bw.

Reference 5

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 17 JUL 1992 to 31 JUL 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (EPA TSCA, 40 CFR 798)

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: EPA TSCA, 40 CFR 798

Deviations:

no

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
- Source: Ave Animals
- Age at study initiation: ~8 weeks
- Weight at study initiation: males: 257 - 278 g; females: 205 - 248 g
- Fasting period before study: 16 to 17 h
- Housing: in cages in groups of five by sex
- Diet: Fresh Purina Rat Chow (Diet #5012), ad libitum
- Water, ad libitum
- Acclimation period: at least one week

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.5 g/mL (20 g of test article was added to corn oil for total volume of 40 mL)

MAXIMUM DOSE VOLUME APPLIED: 1 mL/100 g body weight for non-aqueous vehicles and 2 mL/100 g body weight for aqueous solutions

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 1, 2 and 4 hours post dose and once daily for 14 days toxicity and pharmacological effects, twice daily for 14 days for mortality
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes

Statistics:

The LD50, 95% Confidence limits, dose response curve and slope were calculated, if possible, according to the method of Litchfield and Wilcoxon, 1949 or Horn, 1956.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Remarks on result:

other: no animals died within the 14 days observation period

Mortality:

- no deaths occurred

Clinical signs:

other: - one animal had diarrhea 4 hours post appilcation - in all animals the anogenital area was stained purple on days 1 and 2

Gross pathology:

- all animals were sacrificed at the end
- only in one male animal there was a herniated liver protruding through the diaphragm
- in all other animals no macroscopically visible changes were found

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 item 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.

Executive summary:

Acute oral toxicity of the test item was tested in male and female Wistar rats according to EPA TSCA, 40 CFR 798. The test was conducted administering the limit dose of 5000 mg/kg bw to 5 animals/sex. During the 14 days observation period no animals died and there were no toxicological relevant changes found in necropsy, thus leading to a median lethal dose (LD50) > 5000 mg/kg bw.

Therefore, the test item has not to be classified for acute oral toxicity according to Regulation (EC) No 1272/2008.

Reference 6

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Please refer to attached read across justification document (Chapter 13).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to attached read across document (Chapter 13).

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to attached read across justification document (Chapter 13).

4. DATA MATRIX
Please refer to attached read across justification document (Chapter 13).

Reason / purpose for cross-reference:

read-across source

Sex:

male

Dose descriptor:

LD50

Effect level:

> 11 000 mg/kg bw

Remarks on result:

other: no animals died within the 14 days observation period

Conclusions:

Application of 11000 mg test item per kg bw did not cause lethality in male rats during the 14 day observation period, resulting in a LD50 > 11000 mg/kg bw.
The results of this study are in accordance with the findings presented in the key study.

Executive summary:

Male Crl:CD rats were subjected to test acute oral toxicity. The test substance was administered by gavage at the limit dose of 11000 mg/kg bw to ten rats. During the 14 days observation period no animals died under these conditions, thus leading to a LD50 > 11000 mg/kg bw.

Reference 7

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Please refer to attached read across justification document (Chapter 13).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to attached read across document (Chapter 13).

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to attached read across justification document (Chapter 13).

4. DATA MATRIX
Please refer to attached read across justification document (Chapter 13).

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Remarks on result:

other: no animals died within the 14 days observation period

Mortality:

- no deaths occurred

Clinical signs:

other: - one animal had diarrhea 4 hours post appilcation - in all animals the anogenital area was stained purple on days 1 and 2

Gross pathology:

- all animals were sacrificed at the end
- only in one male animal there was a herniated liver protruding through the diaphragm
- in all other animals no macroscopically visible changes were found

Interpretation of results:

GHS criteria not met

Remarks:

CLP regulation

Conclusions:

Single application of the limit dose of 5000 mg test item 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.

Executive summary:

Acute oral toxicity of the test item was tested in male and female Wistar rats according to EPA TSCA, 40 CFR 798. The test was conducted administering the limit dose of 5000 mg/kg bw to 5 animals/sex. During the 14 days observation period no animals died and there were no toxicological relevant changes found in necropsy, thus leading to a median lethal dose (LD50) > 5000 mg/kg bw.

Therefore, the test item has not to be classified for acute oral toxicity according to Regulation (EC) No 1272/2008.

Reference 8

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Please refer to attached read across justification document (Chapter 13).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to attached read across document (Chapter 13).

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to attached read across justification document (Chapter 13).

4. DATA MATRIX
Please refer to attached read across justification document (Chapter 13).

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No deaths

Clinical signs:

other: Red faeces in all animals from test day 2 to 5 (3 animals) or 6 (3 animals), slightly ruffled fur in 3/6 animals from 30 minutes until 2, 3 or 5 hours (different duration in each of the affected animals) after treatment on day 1.

Gross pathology:

Congestion of the lungs in one animal, but no macroscopic findings in the remaining five animals at scheduled necropsy.

Interpretation of results:

GHS criteria not met

Remarks:

CLP regulation

Conclusions:

The toxicity profile of Pigment Red 202 is assessed based on analogue approaches:
The median lethal dose (LD50) of test item (Pigment Red 122) after a single oral administration to female rats, observed over a period of 14 days, was greater than 2000 mg/kg body weight.

Executive summary:

Two groups, each of three female HanRcc:WIST (SPF) rats, were treated with the test item (Pigment Red 122) by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at a concentration of 0.2 g/mL and administered at a volume dosage of 10 mL/kg.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality / viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period.

Red feces were observed in all animals from test day 2 to 5 or test day 6. Three out of 6 animals were noted with slightly ruffled fur from the observation performed within the first 30 minutes after application to the 2-, 3- or 5 -hour reading.

The body weight of the animals was within the range commonly recorded for this strain and age.

Congestion of the lungs was noted in one animal whereas no macroscopic findings were recorded in the remaining five animals at scheduled necropsy.

The median lethal dose of the test item after single oral administration to female rats, observed over a period of 14 days is:

LD50 (female rat): greater than 2000 mg/kg body weight

Therefore, the test item has not to be classified as acutely toxic by the oral route according to Regulation (EC) No 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 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:

16 January 2007 to 16 March 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF Test data for Registration of Agricultural Chemicals, Test Guidelines, Acute Inhalation Toxicity, 12 NohSan No. 8147, November 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Study in compliance with Swiss Ordinance relating to GLP, which is based on OECD Principles of GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain specifics: HanBrl:WIST(SPF)
- Source: RCC Ltd, Laboratory Animal Services, Füllinsdorf, Switzerland
- Age at study initiation: males: 9 weeks, females: 10 weeks
- Weight at study initiation: males: 232.1-261.6 g, females: 210.0-221.9 g
- Housing: Animals of the same sex were housed in groups of five in Makrolon type IV cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): standard rat maintenance diet, ad libitum, except during the treatment period
- Water (e.g. ad libitum): community tap water ad libitum, except during the treatment period
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5-20 °C
- Humidity (%): 30-72%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Remarks:

flow-past exposure

Vehicle:

other: unchanged (no vehicle)

Mass median aerodynamic diameter (MMAD):

>= 2.64 - <= 2.83 µm

Geometric standard deviation (GSD):

>= 3.93 - <= 4.04

Remark on MMAD/GSD:

MMAD (two measurements)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Similar to the system originally described by Sachsse et al. (1973, 1976) and Cannon et al. (1983)
- Method of holding animals in test chamber: restraint tubes
- Source and rate of air: total airflow: 34 l/min, airflow of the aerosol arriving at the animal ports: 1 l/min per animal port
- System of generating particulates/aerosols: dust aerosol generated from the test item using a rotating brush aerosol generator connected to a micronising jet mill. The aerosol generated was then discharged into the exposure chamber through a 63Ni charge neutraliser.
- Method of particle size determination: gravimetrically (see below)
- Temperature, humidity, oxygen concentration in air chamber: measured on test atmosphere samples collected from the feed tubes in the breathing zone of the animals

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric (weighing the generator cylinder containing the test item before and after the exposure to determine the quantity of test item used. The total weight used during the exposure was then divided by the total airflow volume to give the nominal concentration.
- Samples taken from breathing zone: yes (gravimetric using Millipore filters)

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: measured gravimetrically twice during each exposure using a 7 stage cascade a Mercer Impactor
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): calculated on the basis of the results with the Mercer Impactor
For results, see below

References:
Sachsse, K., L. Ullmann, G. Voss and R. Hess: Measurements of Inhalation Toxicity of Aerosols in Small Laboratory Animals. In: Proceedings of the Europ. Soc. for the Study of Drug Toxicity, Vol. XV, pp. 239-251, Zürich, June 1973.
Sachsse, K., L. Ullmann, K. Zbinden: Toxikologische Prüfungen von Aerosolen im Tierexperiment, "Chemische Rundschau" 29 (1976), No. 38, p. 1.
Cannon, W.C., E.F. Blanton and K.E. McDonald: The Flow-Past Chamber: An Improved Nose-Only Exposure System for Rodents, Am. Ind. Hyg. Assoc. J., 44 (12): 923-928, 1983

Analytical verification of test atmosphere concentrations:

yes

Remarks:

see above

Duration of exposure:

4 h

Remarks on duration:

Approx. 2 h after the start, exposure was interrupted for 3 min (cleaning the exposure system and changing the piston cylinder). Nevertheless, animals were exposed for a total of 4 hours.

Concentrations:

Nominal concentration: 4.419 mg/l
Actual concentration: 3.055 mg/l (± 0.068 mg/l, n = 5), MMAD (two measurements): 2.83 µm (GSD 4.04) and 2.64 µm (GSD 3.93)
Rationale: A target concentration of 3 mg/l air (actual concentration of test item in air) corresponds to the maximum technically feasible aerosol concentration as determined in technical trials.

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days beginning on the day of exposure
- Frequency of observations and weighing: daily for mortality and clinical signs, weiging on days 1 (before exposure), 4, 8 and 15 (day of necropsy)
- Necropsy of survivors performed: yes (all animals)
- Other examinations performed:
clinical signs included, but were not limited to: changes in behaviour, somatomotor activity, body position, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects, e.g. tremors or convulsions, reactivity to handling or sensory stimuli, altered strength, alteration of the skin, fur, nose, eyes and mucous membranes

Statistics:

The LOGIT model was not used as only one group was exposed.

Key result

Sex:

male/female

Dose descriptor:

LC0

Effect level:

3.055 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: mean analytical concentration of five measurements

Mortality:

No mortality, all animals were sacrificed as scheduled on test day 15.

Clinical signs:

other: All animals showed rales, decreased spontaneous activity, hunched posture, tachypnea and ruffled fur on the day of exposure and the two following days in individually variable extent. These signs were not noted from day 4 onwards.

Body weight:

Four females showed a slight transient body weight loss between Day 1 and Day 4. All other animals gained body weight as expected.

Gross pathology:

There were no macroscopic pathology findings in any of the animals. No macroscopically visible coloration of the lungs by Hostaperm Rosa E was detected.

Other findings:

Temperature, relative humidity and oxygen concentration during exposure were considered to be satisfactory for this type of study.

Interpretation of results:

GHS criteria not met

Conclusions:

No mortality was observed after nose-only inhalation exposure to the test item (Pigment Red 122) of male and female rats at the highest technically achievable aerosol concentration of 3.055 mg/L for 4 hours. Based on the lack of lethal effects, severe clinical symptoms indicating a life-threatening or moribund state, and gross morphological abnormalities, it may be reasonably assumed that the LC50 for the test item is greater than 5 mg/l air and that the test item has not to be classified as acutely toxic by the inhalation route according to Regulation (EC) No 1272/2008.

Executive summary:

The purpose of this study was to assess the acute inhalation toxicity of the test item when administered to rats for a single 4-hour period.

One group of five male and five female albino rats [HanBrl:WIST(SPF)], was exposed by nose-only, flow-past inhalation to the test item at mean aerosol concentrations of 3.055 ± 0.068 (n=5) mg/L air (gravimetrically determined). Two gravimetric measurements of particle size distribution during the exposure produced mass median aerodynamic diameters and geometric standard deviations (GSD) of 2.83 µm (GSD 4.04) and 2.64 µm (GSD 3.93), respectively.

All animals were observed for clinical signs and mortality during and following the inhalation exposure, i.e. over a 15-day observation period. Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 4, 8 and 15. All animals were sacrificed and necropsied on day 15.

The ranges of temperature, relative humidity, oxygen content and particle size measured during the exposure were satisfactory for a study of this type.

There were no spontaneous deaths.

All animals showed rales, decreased spontaneous activity, hunched posture, tachypnea and ruffled fur on the day of exposure and the two following days in individually variable extent.

Four females showed a slight transient body weight loss between Day 1 and Day 4. All other animals gained body weight as expected.

There were no macroscopic pathology findings in any of the animals.

In conclusion, at the highest technically achievable aerosol concentration of the test item of 3.055 mg/L air, none of the ten exposed animals died (LC0 = 3.055 mg/L). Based on the lack of lethal effects or severe clinical symptoms indicating a life-threatening or moribund state, it may be reasonably assumed that the LC50 for the test item is likely to be greater than 5 mg/L air.

Therefore, the test item has not to be classified as acutely toxic by the inhalation route 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:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Please refer to attached read across justification document (Chapter 13).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to attached read across document (Chapter 13).

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to attached read across justification document (Chapter 13).

4. DATA MATRIX
Please refer to attached read across justification document (Chapter 13).

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC0

Effect level:

3.055 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: mean analytical concentration of five measurements

Mortality:

No mortality, all animals were sacrificed as scheduled on test day 15.

Clinical signs:

other: All animals showed rales, decreased spontaneous activity, hunched posture, tachypnea and ruffled fur on the day of exposure and the two following days in individually variable extent. These signs were not noted from day 4 onwards.

Body weight:

Four females showed a slight transient body weight loss between Day 1 and Day 4. All other animals gained body weight as expected.

Gross pathology:

There were no macroscopic pathology findings in any of the animals. No macroscopically visible coloration of the lungs by Hostaperm Rosa E was detected.

Other findings:

Temperature, relative humidity and oxygen concentration during exposure were considered to be satisfactory for this type of study.

Interpretation of results:

GHS criteria not met

Conclusions:

The toxicity profile of Pigment Red 202 is assessed based on analogue approaches:
No mortality was observed after nose-only inhalation exposure to the test item (Pigment Red 122) of male and female rats at the highest technically achievable aerosol concentration of 3.055 mg/L for 4 hours. Based on the lack of lethal effects, severe clinical symptoms indicating a life-threatening or moribund state, and gross morphological abnormalities, it may be reasonably assumed that the LC50 for the test item is greater than 5 mg/l air and that the test item has not to be classified as acutely toxic by the inhalation route according to Regulation (EC) No 1272/2008.

Executive summary:

The purpose of this study was to assess the acute inhalation toxicity of the test item when administered to rats for a single 4-hour period.

One group of five male and five female albino rats [HanBrl:WIST(SPF)], was exposed by nose-only, flow-past inhalation to the test item at mean aerosol concentrations of 3.055 ± 0.068 (n=5) mg/L air (gravimetrically determined). Two gravimetric measurements of particle size distribution during the exposure produced mass median aerodynamic diameters and geometric standard deviations (GSD) of 2.83 µm (GSD 4.04) and 2.64 µm (GSD 3.93), respectively.

All animals were observed for clinical signs and mortality during and following the inhalation exposure, i.e. over a 15-day observation period. Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 4, 8 and 15. All animals were sacrificed and necropsied on day 15.

The ranges of temperature, relative humidity, oxygen content and particle size measured during the exposure were satisfactory for a study of this type.

There were no spontaneous deaths.

All animals showed rales, decreased spontaneous activity, hunched posture, tachypnea and ruffled fur on the day of exposure and the two following days in individually variable extent.

Four females showed a slight transient body weight loss between Day 1 and Day 4. All other animals gained body weight as expected.

There were no macroscopic pathology findings in any of the animals.

In conclusion, at the highest technically achievable aerosol concentration of the test item of 3.055 mg/L air, none of the ten exposed animals died (LC0 = 3.055 mg/L). Based on the lack of lethal effects or severe clinical symptoms indicating a life-threatening or moribund state, it may be reasonably assumed that the LC50 for the test item is likely to be greater than 5 mg/L air.

Therefore, the test item has not to be classified as acutely toxic by the inhalation route according to Regulation (EC) No 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC0

Value:

3.055 mg/L air

Quality of whole database:

reliable

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

no classification

Neither in studies witn oral nor inhaltion nor dermal exposure any adverse effects were observed at / above limit doses.