2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[N-(2,4-dimethylphenyl)-3-oxobutyramide]

Endpoint summary

Description of key information

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.

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.

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.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

Value:

> 15 000 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:

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 2

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 .

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC0

Value:

> 4 250 mg/m³ air

Physical form:

inhalation: aerosol

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:

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

Adequacy of study:

key study

Justification for type of information:

See Chapter 13

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

LD0

Effect level:

> 1 710 mg/kg bw

Based on:

act. ingr.

Reference 2

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

Value:

> 1 710 mg/kg bw

Quality of whole database:

reliable with restriction

Justification for classification or non-classification

no classification, The test material did not cause adverse effffects after acute oral, dermal or inhalation exposure at maximal doses (above limit dose)