5-Brom-2-[(3,4,5-trifluorphenoxy)-difluormethyl]-1,3-difluorbenzene

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 20, 2020 - November 10, 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)

Version / remarks:

October 9, 2017

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

5-[(4-bromo-2,6-difluorophenyl)difluoromethoxy]-1,2,3-trifluorobenzene

EC Number:

610-623-5

Cas Number:

511540-64-0

Molecular formula:

C13 H4 Br F7 O

IUPAC Name:

5-[(4-bromo-2,6-difluorophenyl)difluoromethoxy]-1,2,3-trifluorobenzene

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River GmbH, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: no
- Age at study initiation: 13 - 14 weeks
- Weight at study initiation: 224 - 254 g
- Fasting period before study:
- Housing: Single-housed in type III Makrolon cages with a shelter and a play tunnel on softwood bedding material overnight. Because no clinical symptoms were seen one day after treatment the rats were group-housed again in type IV Makrolon cages until end of the observation period.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.0 - 24.1°C
- Humidity (%): 42.7 - 55.3%

Administration / exposure

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: 10% of the total body surface area
- Type of wrap if used: Patch (polypropylene nonwoven) was fixed with a tape (Fixomull stretch)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- For solids, paste formed: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15.
- Necropsy of survivors performed: yes
- Clinical signs including body weight

Results and discussion

Preliminary study:

Due to the chemical properties of the test item, mortality after dermal administration was not expected at the highest starting dose of 2000 mg/kg bw. Therefore, the range-finding study was started in 1 female rat with 2000 mg/kg bw.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: none

Gross pathology:

No organ alterations were identified.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item has no acute dermal toxic potential under the conditions of the present study, and the LD50 value in rats exceeds 2000 mg/kg bw after single dermal administration.

Executive summary:

The objective of the present study was to identify potential toxic effects of the test item after single dermal administration to rats in a stepwise procedure. 

The study was started with a dose-range finding study using one femae rat treated with 2000 mg/kg bw. Due to the fact, that no mortality was seen after treatment with 2000 mg/kg bw, two further females were treated with 2000 mg/kg bw in the main study.

Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy. 

No mortality occurred during the course of this study. No clinical signs of toxicity were observed. The body weight development was inconspicuous throughout the study. The gross pathological examination revealed no organ alterations.

The LD50 value of the test item was determined to be greater than 2000 mg/kg bw.