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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 06 MAR 2012 to 27 MAR 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 423) and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
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
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-[(4-methoxy-2-nitrophenyl)azo]-N-(2-methoxyphenyl)-3-oxobutyramide
EC Number:
229-419-9
EC Name:
2-[(4-methoxy-2-nitrophenyl)azo]-N-(2-methoxyphenyl)-3-oxobutyramide
Cas Number:
6528-34-3
Molecular formula:
C18H18N4O6
IUPAC Name:
2-[(4-methoxy-2-nitrophenyl)diazenyl]-N-(2-methoxyphenyl)-3-oxobutanamide
Test material form:
solid: bulk

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 9-10 weeks
- Weight at study initiation: animals 1-3: 160-165 g, animals 4-6: 155-161 g
- Fasting period before study: 16-19 h
- Housing: The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 110811)
- Diet: Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 0815)
- Water: Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 10
- Air changes (per hr): 10 x
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
cotton seed oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: cotton seed oil was chosen due to its non-toxic characteristics
- Lot/batch no. (if required): MKBG0088V

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
The starting dose was selected to be 2000 mg/kg body weight considering the content of the test substance of 98.3% (w/w). No compound-related mortality was recorded for any animal of step 1 or 2. Based on these results and according to the acute toxic class method regime no further testing was required.
No. of animals per sex per dose:
3 females per step / 2 steps in total
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observation, weighingon day 1, 8, 15
- Necropsy of survivors performed: yes
Statistics:
According to OECD guidelines, the biological relevance of the results is the criterion for the interpretation of results, a statistical evaluation of the results is not regarded as necessary.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: all animals survived until the end of the study without showing any signs of toxicity.
Mortality:
All animals survived until the end of the study.
Clinical signs:
other: None of the animals showed any sign of toxicity.
Gross pathology:
At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the present study, a single oral application of the test item to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality.
The median lethal dose after a single oral administration to female rats, observed over a period of 14 days:
LD50 > 2000 mg/kg body weight
Executive summary:

Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was suspended in the vehicle cottonseed oil at a concentration of 0.2 g/mL and administered at a dose volume of 10 mL/kg.

All animals used in the study were allowed to acclimatise to the laboratory conditions for at least 5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

Table1:  Results per Step

Step

Sex/No.

Dose (mg/kg)

Number of Animals

Number of Intercurrent Deaths

1

female/1-3

2000

3

0

2

female/4-6

2000

3

0

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 treatment-related macroscopic findings were observed in any animal of any step

LD50cut-off: unclassified

Species/strain: WISTAR Crl: WI(Han) rats

Number of animals: 3 per step / 2 steps performed

Vehicle: cottonseed oil

Method: OECD 423
           EC 440/2008, Method B.1 tris
           OPPTS 870.1000
           OPPTS 870.1100


Conclusion:

Under the conditions of the present study, a single oral application of the test item to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality.

 

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

 

LD50cut-off (rat):       unclassified

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

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