1-bromo-3,4,5-trifluorobenzene

Endpoint summary

Description of key information

Skin irritation

Skin irritation was observed in a study according to OECD TG 404 in rabbits (reference 7.3.1 -1).

Eye irritation

The test material produced a severe initial pain reaction in a study according to OECD TG 405 in rabbits. Therefore, the study was terminated (reference 7.3.2 -1).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 24, 1991 to October 01, 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

not specified

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

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: David Percival Ltd., Moston, UK
- Age at study initiation: 12 – 16 weeks
- Weight at study initiation: 2.35 – 2.42 kg
- Housing: individually in suspended metal cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 – 22
- Humidity (%): 57 – 64
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

Up to 72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: On the day before the test each of a group of three rabbits was clipped free of fur from the dorsal/flank area. Only animals with a healthy intact epidermis by gross observation were selected for the study.
On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 mL of the test material was introduced under a 2.5 * 2.5 cm gauze patch and placed in position on the shorn skin
- Type of wrap: The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing: any residual test material removed by gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4h

OBSERVATION TIME POINTS
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined far evidence of primary irritation

SCORING SYSTEM:
- Method of calculation: scored according to Draize (1959).

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

3.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean score

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

The observed effects were fully reversible within 7 days

Other effects:

Other adverse skin reactions noted were haemorrhages of the dermal capillaries, light brown discolouration of the epidermis and oedema extending ventrally below the treatment site. Crust formation was noted at all treated skin sites seven days after treatment.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The test material produced a skin irritation to rabbit skin. No corrosive effects were noted.

Executive summary:

The purpose of this GLP study performed according to OECD TG 404 was to assess the irritancy potential of the test item to the skin of the New Zealand White rabbits. Well-defined erythema was noted at all treated skin sites one hour after patch removal, at the 24 and 48-hour observations and at two treated skin sites at the 72-hour observation. Moderate to severe erythema was noted at one treated skin site at the 72-hour observation. Haemorrhage of the dermal capillaries was noted at two treated skin sites one hour after patch removal. Light brown discolouration of the epidermis was noted at two treated skin sites at the 24 and 48-hour observations and at one treated skin site at the 72-hour observation. Crust formation was noted at all treated skin sites seven days after treatment. Severe oedema was noted at all treated skin sites one and 24 hours after patch removal with moderate to severe oedema at the 48-hour observation and slight to moderate oedema at the 72-hour observation. Oedema extended ventrally below the treatment sites of two animals at the 48-hour observation. In conclusion, the test material produced a skin irritation to rabbit skin. No corrosive effects were noted.

Reference 2

Endpoint:

skin corrosion: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

02-1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

not further specified

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: David Percival Ltd., Moston, UK
- Age at study initiation: 12 – 16 weeks
- Weight at study initiation: 2.98 kg
- Housing: individually in suspended metal cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 – 21
- Humidity (%): 56
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

Due to an initial severe pain reaction the study was terminated immediately after application of the test item.

Observation period (in vivo):

no (see above)

Number of animals or in vitro replicates:

1

Details on study design:

lmmediately before the start of the test, both eyes of the provisionally selected test rabbit were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. A volume of 0.1 mL of the test material was instilled into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after instillation, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. lmmediately after administration of the test material, an assessment of the initial pain reaction was made.

Irritation parameter:

cornea opacity score

Remarks on result:

not determinable

Irritation parameter:

iris score

Remarks on result:

not determinable

Irritation parameter:

conjunctivae score

Remarks on result:

not determinable

Irritation parameter:

chemosis score

Remarks on result:

not determinable

Interpretation of results:

study cannot be used for classification

Conclusions:

The test material produced a severe initial pain reaction. However, as stated by the author of this study there is often no correlation between initial pain reaction and subsequent irritation.

Executive summary:

The purpose of this GLP study performed according to OECD TG 405 was to assess the eye irritancy potential of the test item in New Zealand White rabbits. The application of the test material to the non-irrigated eye of one rabbit produced an initial pain reaction of 4 (max = 5). Therefore, the study was terminated immediately and no further animals were treated. The test material produced a severe initial pain reaction. It was stated that there is often no correlation between initial pain reaction and subsequent irritation.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

A study according OECD TG 404 was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbits. Well-defined erythema was noted at all treated skin sites one hour after patch removal, at the 24 and 48-hour observations and at two treated skin sites at the 72-hour observation. Moderate to severe erythema was noted at one treated skin site at the 72-hour observation. Haemorrhage of the dermal capillaries was noted at two treated skin sites one hour after patch removal. Light brown discolouration of the epidermis was noted at two treated skin sites at the 24 and 48-hour observations and at one treated skin site at the 72-hour observation. Crust formation was noted at all treated skin sites seven days after treatment. Severe oedema was noted at all treated skin sites one and 24 hours after patch removal with moderate to severe oedema at the 48-hour observation and slight to moderate oedema at the 72-hour observation. Oedema extended ventrally below the treatment sites of two animals at the 48-hour observation.In conclusion, the test material produced a skin irritation to rabbit skin. No corrosive effects were noted.

(reference 7.3.1 -1).

Eye irritation

A study according to OECD TG 405 was performed to assess the eye irritancy potential of the test item in New Zealand White rabbits. The application of the test material to the non-irrigated eye of one rabbit produced an initial pain reaction of 4 (max = 5). Therefore, the study was terminated immediately and no further animals were treated. The test material produced a severe initial pain reaction. It was stated that there is often no correlation between initial pain reaction and subsequent irritation (reference 7.3.2 -1).

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available data for skin irritation are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this data, the substance is considered to be classified for skin irritation Cat.2 (H315) under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521. The data for eye irritation are not sufficient for classification purposes under Regulation (EC) No 1272/2008.