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

Endpoint summary

Description of key information

Skin irritation (OECD 404, RL1): female rabbit, not irritating

Eye irritation (OECD 405, RL1): female rabbit, not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 Jun - 07 Aug 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Kisslegg
- Age at study initiation: approx. 27 weeks
- Housing: the rabbits were housed individually in special rabbit cages, with plastic grids placed on mobile racks. The collection pans underneath the cages were cleaned at least 3x per week.
- Diet: Pelleted Provimi Kliba 3418 rabbit maintenance diet, ad libitum (Provimi Kliba AG, Kaiseraugst, Switzerland) and ssniff K snack
- Water: tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 46-77
- Air changes (per hr): air-conditioned room
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

other: not required, untreated sites of the same animal served as the control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
the test material was moistened with some drops of purified water before application

Duration of treatment / exposure:

4 h

Observation period:

72 h
Reading time points: 1, 24, 48 and 72 h and then daily up to experimental day 8.

Number of animals:

3 (females)

Details on study design:

PRETESTS:
Prior to testing, the pH of a preparation of the test material was determined with pH test stripes. The pH was found to be approx. 7.

TEST SITE
- Area of exposure: approximately 6 cm²
- Type of wrap if used: the test substance was applied on the intact, shaved skin on a surgical gauze and the area was covered with a semi-occlusive dressing. The patch was held in place with non-irritating semi-occlusive adhesive tape that was wrapped around the abdomed of the animals.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the patches were removed and any test material residues were wiped off dry
- Time after start of exposure: 4 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- For solids, paste formed: yes

SCORING SYSTEM: Draize scoring system acc. to EEC commission directive 92/69/EEC

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No skin irritation effects were observed; all scores were 0 at all reading time points (after 1 ,24, 48, 72 hours and 7 days) for 3/3 animals.

Other effects:

There was no mortality and no clinical signs of toxicity were observed during the study period. The body weight gains were within the normal ranges during the study period.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present study, no signs of irritations were seen. Therefore, the test item is not considered to be irritating to skin.

Executive summary:

To test for primary skin irritation, 0.5 g of the test material was mixed with some drops of Aqua pro injectione to ensure good contact with the skin. Afterwards the test material was spread onto 6 cm2 patches and applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. The study was started as an initial test with one animal and followed by the confirmatory test with two further animals. The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for further 7 days.

Under the conditions of the present study, no signs of irritations were seen. Therefore, the test item is not considered to be irritating to skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 Jul - 14 Aug 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Kisslegg
- Age at study initiation: approx. 27 weeks
- Housing: the rabbits were housed individually in special rabbit cages, with plastic grids placed on mobile racks. The collection pans underneath the cages were cleaned at least 3x per week.
- Diet: Pelleted Provimi Kliba 3418 rabbit maintenance diet, ad libitum (Provimi Kliba AG, Kaiseraugst, Switzerland) and ssniff K snack
- Water: tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 40-75
- Air changes (per hr): air-conditioned room
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as the control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g (undiluted)
Before the application, the test material was ground in a mortar using a pestle.

Duration of treatment / exposure:

Single application without washing

Observation period (in vivo):

72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals or in vitro replicates:

3 (females)

Details on study design:

PRETESTS:
Prior to testing, the pH of a preparation of the test material was determined with pH test stripes. The pH was found to be approx. 7.

ADMINISTRATION AND DOSE LEVEL
Approx. 24 h before treatment, ophthalmologic examinations were performed using 0.15% fluorescein solution, to ensure that only rabbits with normal eyes were used for the study. Animals with eye defects, injury or irritation were excluded.

0.1 g of the test material was instilled into the conjunctival sac of the left eye of each animal. After instillation the eye lid was closed for approx. 30 seconds.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated eye remained unwashed

SCORING SYSTEM: Draize scoring system. The animals were examined for eye irritation 1 h after tratement, after 24, 48 and 72 hours, and then daily up to day 15 of the experimental part.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No signs of irritation could be observed at the cornea or iris. In animal 1, the conjunctivae showed slight redness at the first and second reading (1 h and 24 h), and slight chemosis at the first reading at 1 h. Further, discharge at the first reading was seen. In animals 2 and 3 similar signs of irritation were seen. The conjunctivae showed slight redness and chemosis at the first reading (1 h). Furthermore, discharge was seen. Thereafter no signs of irritation were observed. The untreated eyes were unchanged.

Other effects:

There was no mortality and no signs of toxicity were observed during the study period. The body weight gains were within the normal ranges during the study period.

Table 1. Individual scores for eye irritation parameters

 

Rabbit #	Time [h]	conjunctivae		iris	cornea
		redness	swelling
1	1	1	1	0	0
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.33	0.0	0.0	0.0
2	1	1	1	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0	0.0	0.0	0.0
3	1	1	1	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0	0.0	0.0	0.0

 

Interpretation of results:

GHS criteria not met

Conclusions:

The test item is not irritating to eye.

Executive summary:

The test item was tested for its eye irritating properties. Prior to testing, the HET-CAM test was performed and no irritating potential could be detected. The test for primary eye irritation was started as an initial test with one animal and followed by the confirmatory test with two further animals.

For the test of primary eye irritation, 0.1 g of the test material was applied into the conjunctival sac of rabbits. The first examination of the eyes followed 1 hour after instillation. The other examinations were performed daily for further 7 days.

No signs of irritation could be observed at the cornea or iris. The conjunctivae showed redness (score 1) at the first (1 hour) and second reading (24 hours) and only in one animal chemosis (score 1) at the first reading (1 hour). Furthermore, discharge (score 1) at the first reading was seen. Thereafter no signs of irritation were observed. The untreated eyes were unchanged.

Except for a slight reddening, chemosis and discharge of the conjunctivae at the first and second reading (24 hours), which were regarded due to mechanical irritation, no signs of irritation was observed. Therefore, the test item should not be regarded as an irritant to the eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In vivo skin irritation study

To test for primary skin irritation, 0.5 g of the test material was mixed with some drops of Aqua pro injectione to ensure good contact with the skin. Afterwards the test material was spread onto 6 cm2 patches and applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. The study was started as an initial test with one animal and followed by the confirmatory test with two further animals. The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for further 7 days.

Under the conditions of the present study, no signs of irritations were seen. Therefore, the test item is not considered to be irritating to skin.

In vivo eye irritation study

The test item was tested for its eye irritating properties. Prior to testing, the HET-CAM test was performed and no irritating potential could be detected. The test for primary eye irritation was started as an initial test with one animal and followed by the confirmatory test with two further animals.

For the test of primary eye irritation, 0.1 g of the test material was applied into the conjunctival sac of rabbits. The first examination of the eyes followed 1 hour after instillation. The other examinations were performed daily for further 7 days.

No signs of irritation could be observed at the cornea or iris. The conjunctivae showed redness (score 1) at the first (1 hour) and second reading (24 hours) and only in one animal chemosis (score 1) at the first reading (1 hour). Furthermore, discharge (score 1) at the first reading was seen. Thereafter no signs of irritation were observed. The untreated eyes were unchanged.

Except for a slight reddening, chemosis and discharge of the conjunctivae at the first and second reading (24 hours), which were regarded due to mechanical irritation, no signs of irritation was observed. Therefore, the test item should not be regarded as an irritant to the eyes.

Justification for classification or non-classification

The available data on skin and eye irritation do not meet the criteria for classification according to Regulation (EC) 1272/2008.