2-(4-(diethylaminopropylcarbamoyl)phenylazo)-3-oxo-N-(2,3-dihydro-2-oxobenzimidazol-5-yl)butyramide

Endpoint summary

Description of key information

Acute toxicity after single oral application was tested in male and female rats, which received 2000 mg/kg bw (5 males, 5 females). All animals survived until the end of the study without showing any signs of toxicity. Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain. At necropsy, no macroscopic findings were observed. The LD50 value for acute oral toxicity is > 2000 mg/kg bw.

A single dermal application of the test item to 10 rats (5 males and 5 females) at a dose of 2000 mg/kg bw was associated with no mortality and neither clinical signs. The dermal LD50 was determined to be > 2000 mg/kg bw

The studies were carried out according to OECD guidelines 401 and 402.

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:

Aug - Sept 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 24 Feb 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

25. April 1984

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Hoe:WISKf

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund, SPF breed
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation:
males: 7 weeks
females: 8 weeks
- Weight at study initiation:
males: 182 g (175-186 g)
females: 177 g (163-185 g)
- Fasting period before study:
16 h before substance application and 3-4 h thereafter
- Housing: in fully air-conditioned rooms in Macrolon cages type 3, on softwood granulate in groups of 5 animals
- Diet (e.g. ad libitum): rat/mice diet Altromin 1324 (Altromin GmbH, Lage/Lippe), ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3°C
- Humidity (%): 50+/-20%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 28. Aug. To: 11. Sept. 1989

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% (w/v)
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: homogeneity of suspension

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 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 weighing: weekly
- clinical observation: 10, 30 60 min, 2, 4, 6 h after application, daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality observed

Clinical signs:

other: no clinical symptoms reported

Gross pathology:

no changes observed

Interpretation of results:

GHS criteria not met

Conclusions:

From the acute oral toxicity study, a LD0 of 2000 mg/kg and a LD50 > 2000 mg/kg bwwas obtained.

Executive summary:

Under the conditions of the present study, a single oral application of the substance to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality. The median lethal dose of the test item after a single oral administration to male and female rats, observed over a period of 14 days is: LD50 cut-off (rat): unclassified In conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC the test item has no obligatory labelling requirement for toxicity. According to Annex I of Regulation (EC) 1272/2008 the test item has no obligatory labelling requirement for toxicity and is not classified. According to GHS (Globally Harmonized Classification System) the test item has no obligatory labelling requirement for toxicity and is not classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

reliable without restrictions

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Sept - Oct 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 24. Feb 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

25. Apr. 1984

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Hoe:WISKf

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation:
males: 8 weeks
females: 9 weeks
- Weight at study initiation:
males: 217 g (214-220 g)
females: 193 g (187-198 g)
- Housing: indiviudally in fully air-conditioned rooms in Macrolon cages type 3, on softwood granulate
- Diet (e.g. ad libitum): rat/mice diet Altromin 1324 (Altromin GmbH, Lage/Lippe), ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3°C
- Humidity (%): 50+/-20%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 19. Sept. To: 3 Oct. 1989

Type of coverage:

occlusive

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Details on dermal exposure:

TEST SITE
- Area of exposure: 6x8 cm
- % coverage: 100
- Type of wrap if used: elastic gauze bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm water
- Time after start of exposure: 24 h after application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): miostened with PEG 400 (1 g test item + 1 mL PEG 400)
- For solids, paste formed: yes

Duration of exposure:

24 h

Doses:

2000 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 and weighing:
body weight: weekly
clinical signs: 30, 60 min, 2, 4, 6 h after application, thereafter daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality observed

Clinical signs:

other: no clinical symptoms reported; applicattion sites were yellow colored

Gross pathology:

no changes observed

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present study, single dermal application of the test item to rats at a dose of 2000 mg/kg body weight was associated with no mortality and neither signs of toxicity nor signs of irritation.The dermal LD50 was determined to be > 2000 mg / kg body weight.

Executive summary:

Under the conditions of the present study, a single dermal application of the substance to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality. The median lethal dose of the test item after a single dermal administration to male and female rats, observed over a period of 14 days is:

LD50 > 2000 mg/kd bw; unclassified In conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC the test item has no obligatory labelling requirement for toxicity. According to Annex I of Regulation (EC) 1272/2008 the test item has no obligatory labelling requirement for toxicity and is not classified. According to GHS (Globally Harmonized Classification System) the test item has no obligatory labelling requirement for toxicity and is not classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

reliable without restrictions

Justification for classification or non-classification

Due to the results described in the acute oral and dermal toxicity studies (LD₅₀oral/dermal in rats > 2000 mg/kg bw) the substance does not have to be classified as acute toxic.