N-(4-{[3-(dimethylamino)propyl]sulfamoyl}phenyl)-2-[(2-methoxy-4-nitrophenyl)diazenyl]-3-oxobutanamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: JMAFF Nousan 8147 2-1-1

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-(4-{[3-(dimethylamino)propyl]sulfamoyl}phenyl)-2-[(2-methoxy-4-nitrophenyl)diazenyl]-3-oxobutanamide

EC Number:

700-222-4

Cas Number:

1065519-44-9

Molecular formula:

C22H28N6O7S

IUPAC Name:

N-(4-{[3-(dimethylamino)propyl]sulfamoyl}phenyl)-2-[(2-methoxy-4-nitrophenyl)diazenyl]-3-oxobutanamide

Constituent 2

Reference substance name:

No. 408 Yellow

IUPAC Name:

No. 408 Yellow

Details on test material:

- Name of test material (as cited in study report): No. 408 Yellow
- Physical state: yellow powder
- Analytical purity: 98.6%
- Purity test date: 07 November 2008
- Lot/batch No.: 081105-1
- Expiration date of the lot/batch: 04 November 2009
- Stability under test conditions:
- Storage condition of test material: room temperature, dark, sealed container
- Other: Source: TOYO INK MFG. CO. LTD.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 162 - 196 g
- Fasting period before study: overnight until 3 hours after dosing
- Housing: 3/group
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No.1, Special Diets Services Ltd, Witham, UK; ad libitum except fasting period
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 to 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 40 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: aqueous methyl cellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 and 500 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: test article did not dissolve or suspend in purified water


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Since there were no data to indicate that deaths my occur at dose levels of less than 2000 mg/kg, the first dose level was 2000 mg/kg.

Doses:

2000 and 5000 mg/kg

No. of animals per sex per dose:

2000 mg/kg: 6 females
5000 mg/kg: 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: clinical signs immediately post-dose, at 15 and 30 minutes post-dose, hourly betwen 1 to 4 hours post-dose (inclusive), twice daily on days 2, 3 and 4 and once daily from day 5 to 15; weighing on day -1 (before dosing) and on days 1, 4, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Not required by guideline.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortality occurred

Clinical signs:

2000 mg/kg bw: piloerection in 3/6 on the day of dosing
5000 mg/kg bw: piloerection in 3/3 from 1 h after dosing and lasting up to day 8, hunched posture in 1/3 from day 2 to 4, orange coloured faeces in 2/3 from day 4 to 7

Body weight:

All rats gained weight during the first and second week of the observaion period, except for one animal at 2000 mg/kg which showed a slight body weight loss during the second week.

Gross pathology:

2000 mg/kg bw: dark or pale foci on the lungs of 2/6 rats, 1/6 had a red and distended bladder with a prominent vascular structure.
5000 mg/kg: no abnormalities observed.

Any other information on results incl. tables

Conclusion:

The acute median lethal oral dose level of the test article, No. 408 Yellow, was found to exceed 5000 mg/kg.

The test article did not need to be classified according to the Globally Harmonised System for the classification of chemicals which cause acute toxicity.

The test material was considered to have no significant acute toxic risk if swallowed and did not meet the criteria for classification according to Commission Directive 2001/59/EC.