4-[difluoro(3,4,5-trifluorophenoxy)methyl]-2',3,5-trifluoro-4''-propyl-1,1':4',1''-terphenyl

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-04-19 to 2007-08-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 17 December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Principles of method if other than guideline:

None

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-{4-[difluoro(3,4,5-trifluorophenoxy)methyl]-3,5-difluorophenyl}-3-fluoro-4'-propyl-1,1'-biphenyl

EC Number:

619-490-8

Cas Number:

303186-36-9

Molecular formula:

C27H22F8O2

IUPAC Name:

4-{4-[difluoro(3,4,5-trifluorophenoxy)methyl]-3,5-difluorophenyl}-3-fluoro-4'-propyl-1,1'-biphenyl

Test material form:

solid: bulk

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Test system
Species: Rat, Wistar HsdCpb: WU, males (m) and females (f)
Breeder: F. Winkelmann, 33178 Borchen
Age: approx. 7 to 8 weeks

- Identification and adaptation
Healthy young animals were allocated to the study group at least 7 days before dosing to allow for acclimatization.
The rats were identified by an ear tattoo.

- Housing and diet
The rats were housed in an air-conditioned room of about 25 m^2 in the Institute of Toxicology. Lighting was controlled by a timer to provide a 12 hour light - 12 hour dark regime.

The rats were kept separately in type III Makrolon cages with a shelter, placed on mobile racks. Conventional softwood granulate was used
as the bedding. One day before treatment, and up to 24 hours after dosing, metal grids were placed above the softwood granulate.
The cages and the metal grids had been machine-cleaned before the start of the experimental part. The bedding was changed two times per
week.

Temperature and humidity were measured using a thermohygrograph. The room temperature during the experimental period was 19 to 23 °C
and the relative atmospheric humidity 46 to 73 %.

Diet was withheld from 17 hours before until up to 4 hours after treatment. At all other times food and tap water from Makrolon drinking
bottles were available to the rats ad libitum.

According to the specifications given by the manufacturer, the diet, Provimi Kliba 3433.0, had been checked by independent laboratories.
Analysis included qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics.
The drinking water was periodically analyzed according to the German regulations for human drinking water.

The softwood granulate was analytically checked by independent laboratories.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: see section Details on Test Materials

Doses:

2000 mg/kg bw (limit test)

No. of animals per sex per dose:

3 (m) / 3 (f)

Control animals:

no

Details on study design:

according to Guideline

Statistics:

n.a.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality observed. All rats survived the observation period.

Clinical signs:

No signs of toxicity were detected in the 3 male and 3 female rats after treatment with 2000 mg/kg of the test item.

Body weight:

Body weight development of the treated rats was inconspicuous.

Gross pathology:

At necropsy no organ alterations were seen.

Other findings:

None

Any other information on results incl. tables

No signs of toxicity were detected in the 3 male and 3 female rats after treatment with 2000 mg/kg bw of the test material.

All rats survived the observation period. Body weight development of the treated rats was inconspicuous. At necropsy no organ alterations were seen.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the result of this study, it is concluded, that the test material has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg bw following oral treatment in rats. The test material can be allocated to ATC class 0 i.e. the LD50 value is expected to exceed 2000 mg/kg.

Executive summary:

Purpose

The purpose of this assay was to provide information on possible health hazards for the test material and serve as a rational basis for risk assessment to the potential of acute oral toxicity of the test item in man.

Study design

The test material was tested for acute toxicity in rats after oral administration of 2000 mg/kg body weight. Directly before the administration the test material was prepared with aqueous Methocel K4M Premium solution as vehicle.

This study was performed according to the ,Acute toxic class method" (ATC).

Results

No signs of toxicity were seen in the rats (3 males and 3 females) after treatment with 2000 mg/kg. The body weight development was inconspicuous throughout the study. There were no deaths during the course of the study.

The gross pathological examination revealed no organ alterations.

Conclusions

According to the results of this study the test material can be allocated to ATC class 0 i.e. the LD50 value is expected to exceed 2000 mg/kg.