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

Endpoint summary

Description of key information

acute toxicity, oral (OECD 423, RL1), rats (m/f): LD50 > 2000 mg/kg bw

acute toxicity, dermal (OECD 402, RL1), rats (f): LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 Jun 2006 - 14 Aug 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann, 33178 Borchen
- Age at study initiation: about 6-7 weeks
- Weight at study initiation: 158 - 180 g (range)
- Fasting period before study: yes, overnight (17 hours before - 4 h after treatment)
- Housing: the rats were housed in an air-conditioned room of ca. 25 m² in the Institute of Toxicology in Macrolon cages type III with a shelter, placed on mobile racks. Animals were kept on conventional softwool granulate as bedding which was changed 2x per week.
- Diet: Provimi Kliba 3433.0, ad libitum
- Water: tap water from Makrolon drinking bottles, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 45-75
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw
Directly before the preparation the test metariel was solved in the vehicle using a shaking device (Vortex Genie) and and Ultra Turrax device.

The vehicle chosen was Methocel(R) K4M Premium solution (Batch ZDP 24/2006 and 26/2006, stable until June 30 and July 14 2006)

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
The behaviour and general condition of all animals was monitored for at least 6 h after administration of the test material and then checked daily. All animals were weighed before treatment and on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.
- Necropsy of survivors performed: yes, all surviving animals were sacrificed at the end of the experimental period by CO2 asphyxia and subjected to gross pathological investigation.

Statistics:

Body weight data were recorded with the PC software "akudat", the statistical evaluation of the body weight were carried out with the software "Tox 511A", the body weight development of each rat and group was determined. The group mean value was calculated for each measurement.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality during the study period.

Clinical signs:

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

Gross pathology:

Necropsy revealed no substance-related findings.

Table 1: Mortality and clinical signs during the study period

 

Dose [mg/kg bw]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)
Males & Females
2000	0/0/6	---	---	0
LD50 > 2000 mg/kg bw

                                                                                           

* first number = number of dead animals                                 

 second number = number of animals with clinical signs         

 third number = number of animals used                               

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study, it is concluded that the test item has no acute toxic potential and the the LD50 value is higher than 2000 mg/kg bw after oral treatment in rats.

Executive summary:

The test material was tested for acute toxicity in rats after oral administration of 2000 mg/kg bw. Directly before administration the test material was prepared with aqueous Methocel Premium Solution as the vehicle. The study was performed according to OECD Guideline 423.

No signs of toxicity were detected in the rats (3 males and 3 females) after treatment with 2000 mg/kg bw. The body weight development was inconspicuous. There were no deaths during the course of the study. The gross pathological examination revealed no organ alterations.

Based on the results of this study, it is concluded that the test item has no acute toxic potential and the the LD50 value is higher than 2000 mg/kg bw after oral treatment in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

OECD Guideline study under GLP conditions

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

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

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%

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

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.

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.

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. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

OECD Guideline study under GLP conditions

Additional information

Acute oral toxicity

The test material was tested for acute toxicity in rats after oral administration of 2000 mg/kg bw. Directly before administration the test material was prepared with aqueous Methocel Premium Solution as the vehicle. The study was performed according to OECD Guideline 423.

No signs of toxicity were detected in the rats (3 males and 3 females) after treatment with 2000 mg/kg bw. The body weight development was inconspicuous. There were no deaths during the course of the study. The gross pathological examination revealed no organ alterations.

Based on the results of this study, it is concluded that the test item has no acute toxic potential and the the LD50 value is higher than 2000 mg/kg bw after oral treatment in rats.

Acute dermal toxicity

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.

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. 

 

Justification for classification or non-classification

The available data on acute oral and dermal toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008.