6-(2-chloro-6-cyano-4-nitrophenylazo)-4-methoxy-3-[N-(methoxycarbonylmethyl)-N-(1-methoxycarbonylethyl)amino]acetanilide

Endpoint summary

Description of key information

The acute oral toxicity study was performed to assess the acute oral toxicity of the test item in rat HanIbm: WIST (SPF). 
The acute dermal toxicity study was performed to asses the acute dermal toxicty of the test item, (FAT 41024/B TE), in rat HanIbm: WIST (SPF).

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:

22 December 1998 to 14 January 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP methodology followed and OCED guideline 423 used to performed the experiment.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other 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)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Rat HanIbm: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: RCC Ltd, Biotechnology & Animal Breeding Division, CH-4414 Füllinsdorf / Switzerland
- Age when treated: 8 weeks (male) and 10 weeks ( female)
- Body weight rage when treated: 200.7-214.8 g (male) and 176.6-184.2 (female)
- Identification: By unique cage number and corresponding color-coded spots on the tail.
- Acclimatization: 7 days week under laboratory conditions, after health examination.
- Diet: ad libitum
- Water : ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%):40-70%
- Air changes (per hr):10-15 air changes per hour
- Photoperiod (hrs dark / hrs light):12 hour light and 12 hour dark, music was palyed for approximately 8 hours during the light period.

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

(PEG 300)

Details on oral exposure:

Test article preparation:
The test article was placed into a glass beaker on a tared Mettler PG 503-S balance and the vehicle (polyethylene glycol PEG 300) was added. A weight by volume dilution was prepared using a glass rod and magnetic stirrer as homogenizer. Homogeneity of the test article in the vehicle was maintained during treatment. The preparation was made shortly before each dosing.

Doses:

Dose / kg body weight: 2000 mg
Application volume / kg body weight: 10 ml

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Four times during test day 1 and once daily during days 2-15
Body weight: On test day 1 (pre-administartion), 8 and 15.
Clinical signs: Each animal was examined for changing in appearance and behaviour four times during day 1, and once daily during days 2-15. All abnormalities were reccorded.
- Necropsy of survivors performed: yes Necropsy were performed by experineced prosectors. At the end of teh observation period all animals were sacrified by intrperitoneal injection of NARCOREN at a dose of at least 2.0ml/kg body weight (equivalent to at least mg sodium pentobarbitone/kg body weght)
- Other examinations performed: clinical signs, body weight.

Statistics:

No statistical analysis was used as no deaths occured.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occured during the study

Clinical signs:

other: No clinical signs of toxicity were observed during the study period.

Gross pathology:

No macroscopic findings were observed at necropsy.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The median lethal dose of FAT 41024/B after single administartion to rats of both sexes, observed over a period of 14 days, could not be estimated as no death occured.
LD50 is greater than 2000 mg/kg.

Executive summary:

The purpose of this study was to assess the acute oral toxicity of FAT 41024/B when administred by single oral gavage to rats, followed by an observation period of 14 days.

The experiment was performed according to the OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

Two groups , each using three male or three female HanIbm: WIST (SPF) rats, were treated with FAT 41024/B at 2000 mg/kg by oral gavage.

The test article was suspended in vehicle (PEG 300) at a concentration of 0.2 g/ml and administred at a volume of 10 ml/kg. The animals were examined for clinical signs four times during test day 1 and once daily during test days 2 -15.

Mortaliy/Viability were reccorded together with clinical signs at the same time intervals. Body weight were recorded on day 1 prior to administartion and on day 8 and 15.

All animals were necropsied and examined macroscopically.

No deaths occured during the study.

No clinical signs of toxicity were observed during the study period.

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

No macroscopic findings were observed at necropsy.

In conclusion, The median lethal dose of FAT 41024/B after single administartion to rats of both sexes, observed over a period of 14 days, could not be estimated as no death occured. LD50 is greater than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

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:

20 January 1999 to 10 February 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP methodology followed and OCED guideline 402 used to performed the experiment.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: HanIbm: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, CH-4414 Switzerland
- Age when treated: 9 weeks (male) and 12 weeks (female)
- Body weight rage when treated: 230.9-246.8 g (male) and 193.5-206.1 g (female)
- Identification: By unique cage number and corresponding color-coded spots on the tail.
- Acclimatization: 7 days under laboratory conditions, after health examination.
- Diet: ad libitum
- Water : ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%):40-70%
- Air changes (per hr):10-15 air changes per hour
- Photoperiod (hrs dark / hrs light):12 hour light and 12 hour dark, music was palyed approximately 8 hours during the light period.

Type of coverage:

semiocclusive

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on dermal exposure:

TEST SITE
- Area of exposure: Backs of the animals
- % coverage: 10% of the total body surface
- Type of wrap if used: semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
24 hours after the application the dressing was removed and the skin was washed with lukewarm tap water and dried with disposable paper towels.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4.0 ml. The test article was prepared in vehicle PEG 300

Duration of exposure:

24 hours

Doses:

Rats were treated with FAT 41024/B at 2000 mg/kg by dermal application.

No. of animals per sex per dose:

5 males and 5 females.

Control animals:

yes, concurrent vehicle

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Four times during test day 1 and once daily during days 2-15
Body weight: On test day 1 (pre-administartion), 8 and 15.
Clinical signs: Each animal was examined for changing in appearance and behaviour four times during day 1, and once daily during days 2-15. All abnormalities were reccorded.
- Necropsy of survivors performed: yes Necropsy were performed by experineced prosectors. At the end of teh observation period all animals were sacrified by intrperitoneal injection of NARCOREN at a dose of at least 2.0 ml/kg body weight (equivalent to at least 320mg sodium pentobarbitone/kg body weight)
- Other examinations performed: clinical signs, body weight.

Statistics:

No statistical analysis was used as no deaths occured.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occured during the study.

Clinical signs:

other: In all animals, residual test article was observed on the treated skin on test day two and persisted in two females until test day 14. No systemic signs of toxicity were observed during the study period.

Gross pathology:

No macroscopic finding were observed at necropsy.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The median lethal dose of FAT 41024/B after single dermal administartion to rats of both sexes, observed over a period of 14 days, could not be estimated as no deaths occured. LD50 is greater than 2000 mg/kg.

Executive summary:

The purpose of this study was to assess the acute dermal toxicty of FAT 41024/B when administred to rats by a single semi-occlusive dermal application, followed by an observation period of 14 days.

This experiment was performed according to the OECD Guideline 402 (Acute Dermal Toxicity).

A group of five male and five female HanIbm: WIST (SPF) rats was treated with FAT 41024/B at 2000 mg/kg by dermal application. The test article was prepared in vehicle (PEG 300) at a concentration of 0.5 mg/ml and administred at a volume of 4 ml/kg. The animals were examined for clinical signs four times during day 1 and once daily during days 2 -15.

Mortality /Viability were recorded together with clinical signs at the same time intervals.

Body weight were recorded on day 1 prior to administration and on days 8 and 15.

All animals were necropsied and examined macroscopically.

No deaths occured during the study.

In all animals, residual test article was observed on the treated skin on test day two and persisted in two females until test day 14. No systemic signs of toxicity were observed during the study period.

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

No macroscopic findings were observed at necropsy.

The median lethal dose of FAT 41024/B after single dermal administartion to rats of both sexes, observed over a period of 14 days, could not be estimated as no deaths occured. LD50 is greater than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

The acute oral toxicity study was performed in male and female rats and the test substance was applied at a dose level of 2000 mg/kg. No death occured during the study.The Oral LD50 was therefore considered to be greater than 2000 mg/kg.

An acute dermal toxicity was conducted with rats (5 males and 5 females) at a dose level of 2000 mg/kg. The substance was applied to the intact skin during 24 hours and no death occured during the study and following observation period. The acute dermal LD50 in rabbit is considered to be greater than 2000 mg/kg.

Justification for selection of acute toxicity – oral endpoint
Only this study in available

Justification for selection of acute toxicity – dermal endpoint
Only this study is available

Justification for classification or non-classification

Based on the above mentioned results the substance does not need to be classified according to CLP regulation (Regulation EC No.1272/2008) and DSD (Directive 67/548/EEC).