3,3'-[(4-{(E)-[2-bromo-4-nitro-6-(trifluoromethyl)phenyl]diazenyl}phenyl)imino]dipropanenitrile

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 29-FEB-2000 to 15-MAY-2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guidance test with GLP compliance

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

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:

other: Directive 96/54/EEC, B.1 tris "Acute Toxicity-Oral-Acute Toxic Class Method", September 30, 1996.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Identification: FAT41'029/A
Batch number: ARL 123/PP 1/99 UL
Purity: approx. 98 %
Color / Physical form: orange red to brown powder
Stability of test article: Stable under storage conditions
Expiry date: 04-NOV-2005
Stability of test article dilution: For at least 24 hours in polyethylene glycol at room temperature
Storage conditions: In the original container, at room temperature (range of 20 ± 3 °C), away from direct sunlight
Safety precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel

Test animals

Species:

rat

Strain:

other: HanIbm: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST SYSTEM
Test system: Rat, HanIbm: WIST (SPF)
Source: RCC Ltd, Biotechnology & Animal Breeding Division, Wölferstrasse 4, CH-4414 Füllinsdorf / Switzerland
Number of animals per group: 3 males or 3 females
Age when treated: Males: 11 weeks; Females: 8-10 weeks
Body weight range when treated: Males: 152.7-188.4 g; Females: 147.4 - 165.5 g
Acclimatization: One week under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

HUSBANDRY
Conditions
Standard Laboratory Conditions:
Air-conditioned with 10-15 air changes per hour and continuously monitored environment with a range for room temperature of 22 ± 3 °C, and for relative humidity between 30-45 %. The animals were provided with a 12-hour artificial fluorescent light, 12-hour dark cycle. Music was played during the light period.
Accommodation: Groups of three in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz)
Diet: Pelleted standard Kliba 3433, batch no.43/99 rat maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst) available ad libitum (except for the overnight fasting period prior to intubation).
Water: Community tap water from Füllinsdorf, available ad libitum.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

The animals received a single dose of the test article on a 2000 mg/kg body weight basis by oral gavage following fasting for 18 hours, but with free access to water. Food was provided again 3 hours after dosing.
Dose / kg body weight: 2000 mg
Application volume / kg body weight: 10 ml

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

TEST ARTICLE PREPARATION
The test article was placed into a glass beaker on a tared Mettler PM 460 balance and the vehicle (polyethylene glycol, PEG 300) was added. A weight by volume dilution was prepared using a magnetic stirrer as homogenizer. Homogeneity of the test article in the vehicle was maintained during treatment. The preparation was made shortly before each dosing.
OBSERVATIONS
Mortality / Viability: One, two, three and five hours after test article administration on test day 1 and twice daily during days 2-15.
Body weights: On test days 1 (pre-administration), 8 and 15.
Clinical signs: Each animal was examined for changes in appearance and behaviour four times during day 1, and once daily during days 2-15. All abnormalities were recorded.
PATHOLOGY
NECROPSY
Necropsies were performed by experienced prosectors. At the end of the observation period all animals were sacrificed by intraperitoneal injection of NARCOREN (Rhône Mérieux GmbH, D-88471 Laupheim) at a dose of at least 2.0 ml/kg body weight (equivalent to at least 320 mg sodium pentobarbitone/kg body weight). The animals were examined macroscopically and all abnormalities recorded. Thereafter, they were discarded.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No death occurred during the study.

Clinical signs:

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

Gross pathology:

No macroscopic findings were observed at necropsy.

Other findings:

no data

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results of the test, LD50 (rat, oral) is greater than 2000 mg/kg.

Executive summary:

The acute oral toxicity test was performed according to OECD guideline No. 423 and Directive 96/54/EEC, B.1 under GLP compliance. Two groups, each using three male or three female HanIbm: WIST (SPF) rats, were treated with FAT 41'029/A at 2000 mg/kg by oral gavage. The test article was suspended in vehicle (polyethylene glycol, PEG 300) at a concentration of 0.2 g/ml and administered 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. Mortality/viability were recorded together with clinical signs at the same time intervals and twice daily during test days 2-15. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically.

No death occurred during the study. No clinical signs were observed during the observation period. Two male animals (nos. 4 and 6) showed a marginal loss of body weight (-5 %) between test day 8 and 15. The body weight of the other animals was within the range commonly recorded for animals of this strain and age. No macroscopic findings were observed at necropsy. Thus, the LD50 of FAT 41'029/A after single oral administration to rats of both sexes, observed over a period of 14 days, is greater than 2000 mg/kg body weight.