N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-2-[(4-nitrophenyl)azo]-3-oxobutyramide

Endpoint summary

Description of key information

Single application of 15000 mg/kg bw of the test substance 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 Wistar rats to 1274 mg/m³ test item (i.e. maximum technically feasible concentration) for 4 hours did not result in the death of the animals during a 14 day observation period, resulting in a LC50 value of > 1274 mg/m³.

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 31 AUG 1976 to 21 SEP 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Remarks:

study was performed previous to GLP implementation

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
- Weight at study initiation: 100-120 g
- Fasting period before study: 16 h before dosing, 2 h after
- Diet: ALTROMIN 1324 (Altroge, Lage, 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 %

Doses:

15 000 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 observations and weighing: weekly
- Necropsy of survivors performed: yes

Sex:

female

Dose descriptor:

LD50

Effect level:

> 15 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no animal died within the observation period

Gross pathology:

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

Other findings:

Test substance was excreted via the faeces.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Single application of 15000 mg/kg bw of the test substance 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. 15000 mg/kg bw of the test substance were administered by gavage. No animal died during the 14 day observation period, thus leading to a LD50 > 15000 mg/kg bw.

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:

experimental study

Adequacy of study:

key study

Study period:

From 5 May 1981 to 19 MAY 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Relevant methodological deficiencies, poor documentation

Qualifier:

according to guideline

Guideline:

other: Company guideline

Deviations:

no

Principles of method if other than guideline:

test for acute toxicity after inhalation exposure (dust exposure in open, dynamic system)

GLP compliance:

no

Remarks:

study was performed previous to GLP implementation

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: own breed
- Weight at study initiation: males: mean 199 g (range: 196 to 201 g); females: mean 205 g (range: 195 to 216 g)
- Housing: plastic cages
- Diet: Standard husbandry diet Altromin 1324 (Altromin GmbH, Lage/Lippe, Germany), ad libitum
- Water: tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 °C (in exposure cylinder)
- other measurmenst during dust exposure: 21% oxygen, 5000 ppm carbon dioxid, no carbon monoxide

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical plastic cage
- Exposure chamber volume: 60 L
- Method of holding animals in test chamber: each animal was in a plastic tube
- Source and rate of air: laminar air stream of 900 L/hour at 1 bar from above
- System of generating particulates/aerosols: dustgenerator "Wright Dust Feed Mechanism" of L. Adams Ltd., London, UK
- Treatment of exhaust air: exhaust device at the basement of the exposure chamber in line with a diverse system of filters

TEST ATMOSPHERE ANALYSIS
- Brief description of analytical method used: gravimetric measurement: The test atmosphere was sucked through filters ("Experimentiertrommelgasfilter", Elster AG, Mainz-Kastel, Germany; as well as a fibre glass and a membrane filter (diameter of pores 0.65 µm) Sartorius Membranfilter GmbH, Göttingen, Germany) by means of vacuum (at 1200 L/h). The exhaust quantity was 10 L/min. The filters were positioned in an exsiccator 24 h before use. The filters were weighed before and after each measurement by means of electrical scales (Sartorius-Werke GmbH, Göttingen, Germany).
- Waste treatment: After the filters 2 washing bottles, filled with water and polyglycol 400, were placed. Dust leaving the test chanmber due to high pressure was sucked into a gas cleaning station.

TEST ATMOSPHERE
- Particle size distribution: > 0.65 µm

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric measurement

Duration of exposure:

4 h

Concentrations:

mean: 1274 mg/cubic metre air
range: 521 to 2511 mg/cubic metre air
Concentration applied was the maximum technically feasible concentration.

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily except on weekends
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1 274 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: maximum feasible concentration tested; no animals died within the 14 day observation period

- no deaths occurred

- during dust exposure rats showed unsteady breathing

- behaviour of the rats was normal during the 14 days observation period

- body weight development was normal during the 14 days observation period

- no gross organ changes were seen at necropsy

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Exposure of male and female Wistar rats to 1274 mg/m³ test item (i.e. maximum technically feasible concentration) for 4 hours did not result in the death of the animals during a 14 day observation period, resulting in a LC50 value of > 1274 mg/m³.

Executive summary:

Acute inhalation toxicity of the test item has been investigated in male and female Wistar rats. Mean dust exposure concentration was 1274 mg test substance per cubic metre (i.e. maximum technically feasible concentration; exposure ranged from 521 to 2511 mg/ cubic metre). The rats were exposed for 4 hours, nose only. 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 > 1274 mg/m³ for the inhalation of dust.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Study period:

From 5 May 1981 to 19 MAY 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Relevant methodological deficiencies, poor documentation

Justification for type of information:

See read across justification document in chapter 13

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: Company guideline

Deviations:

no

Principles of method if other than guideline:

test for acute toxicity after inhalation exposure (dust exposure in open, dynamic system)

GLP compliance:

no

Remarks:

study was performed previous to GLP implementation

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: own breed
- Weight at study initiation: males: mean 199 g (range: 196 to 201 g); females: mean 205 g (range: 195 to 216 g)
- Housing: plastic cages
- Diet: Standard husbandry diet Altromin 1324 (Altromin GmbH, Lage/Lippe, Germany), ad libitum
- Water: tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 °C (in exposure cylinder)
- other measurmenst during dust exposure: 21% oxygen, 5000 ppm carbon dioxid, no carbon monoxide

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical plastic cage
- Exposure chamber volume: 60 L
- Method of holding animals in test chamber: each animal was in a plastic tube
- Source and rate of air: laminar air stream of 900 L/hour at 1 bar from above
- System of generating particulates/aerosols: dustgenerator "Wright Dust Feed Mechanism" of L. Adams Ltd., London, UK
- Treatment of exhaust air: exhaust device at the basement of the exposure chamber in line with a diverse system of filters

TEST ATMOSPHERE ANALYSIS
- Brief description of analytical method used: gravimetric measurement: The test atmosphere was sucked through filters ("Experimentiertrommelgasfilter", Elster AG, Mainz-Kastel, Germany; as well as a fibre glass and a membrane filter (diameter of pores 0.65 µm) Sartorius Membranfilter GmbH, Göttingen, Germany) by means of vacuum (at 1200 L/h). The exhaust quantity was 10 L/min. The filters were positioned in an exsiccator 24 h before use. The filters were weighed before and after each measurement by means of electrical scales (Sartorius-Werke GmbH, Göttingen, Germany).
- Waste treatment: After the filters 2 washing bottles, filled with water and polyglycol 400, were placed. Dust leaving the test chanmber due to high pressure was sucked into a gas cleaning station.

TEST ATMOSPHERE
- Particle size distribution: > 0.65 µm

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric measurement

Duration of exposure:

4 h

Concentrations:

mean: 1274 mg/cubic metre air
range: 521 to 2511 mg/cubic metre air
Concentration applied was the maximum technically feasible concentration.

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily except on weekends
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1 274 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: maximum feasible concentration tested; no animals died within the 14 day observation period

- no deaths occurred

- during dust exposure rats showed unsteady breathing

- behaviour of the rats was normal during the 14 days observation period

- body weight development was normal during the 14 days observation period

- no gross organ changes were seen at necropsy

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Exposure of male and female Wistar rats to 1274 mg/m³ test item (i.e. maximum technically feasible concentration) for 4 hours did not result in the death of the animals during a 14 day observation period, resulting in a LC50 value of > 1274 mg/m³.

Executive summary:

Acute inhalation toxicity of the test item has been investigated in male and female Wistar rats. Mean dust exposure concentration was 1274 mg test substance per cubic metre (i.e. maximum technically feasible concentration; exposure ranged from 521 to 2511 mg/ cubic metre). The rats were exposed for 4 hours, nose only. 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 > 1274 mg/m³ for the inhalation of dust.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC0

Value:

1 274 mg/m³ air

Physical form:

inhalation: dust / mist

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 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 study available

Justification for classification or non-classification

No classification

The test item did not cause adverse effects after oral and inhalation exposure.