(pentabromophenyl)methyl acrylate

Endpoint summary

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:

09/04/2003-17/04/2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP comparable to OECD guideline

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Qualifier:

according to guideline

Guideline:

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

Principles of method if other than guideline:

/

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 Perceval Ltd., Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2-3.5 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):17-23°C
- Humidity (%):30-70%
- Air changes (per hr):15
- Photoperiod (hrs dark / hrs light): 12hrs dark/12hrs light

Type of coverage:

other: in an elasticated corset

Preparation of test site:

other: clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

3minutes, 1 hour (for 1 rabbit) and 4 hours after application (for all)

Observation period:

72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure:on the back
- Type of wrap if used: cotton gauze patch, placed in position with a strip or surgical adhesive tape and wrapped in an elasticated corset

REMOVAL OF TEST SUBSTANCE
- Washing (if done): by gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 3 min, 1 hour, 4 hours

SCORING SYSTEM: Draize
Erythema and Eschar formation: 0-4
Oedema formation: 0-4

Irritation parameter:

erythema score

Basis:

other: total

Time point:

other: 1 hour

Score:

3

Max. score:

12

Irritation parameter:

erythema score

Basis:

other: total

Time point:

other: 24 hours

Score:

3

Max. score:

12

Irritation parameter:

erythema score

Basis:

other: total

Time point:

other: 48 hours

Score:

1

Max. score:

12

Irritation parameter:

erythema score

Basis:

other: total

Time point:

other: 72 hours

Score:

0

Max. score:

12

Irritation parameter:

edema score

Basis:

other: total

Time point:

other: 1 hour

Score:

3

Max. score:

12

Irritation parameter:

edema score

Basis:

other: total

Time point:

other: 24 hours

Score:

3

Max. score:

12

Irritation parameter:

edema score

Basis:

other: total

Time point:

other: 48 hours

Score:

0

Max. score:

12

Irritation parameter:

edema score

Basis:

other: total

Time point:

other: 72 hours

Score:

0

Max. score:

12

Irritation parameter:

primary dermal irritation index (PDII)

Time point:

other: 72 hours

Score:

1

Max. score:

8

Irritant / corrosive response data:

4 -hour exposure: Very slight erythema and very slight oedema were noted at all treated skin sites one and 24 hours after patch removal. Very slight erythema persisted at one treated skin site at the 48-hour observation. Two treated skin sites appeared normal at the 48-hour observation and one treated skin site appeared normal at the 72-hour observation.
1 -hour exposure: No evidence of skin irritation was noted during the study.
3 -minute exposure period: No evidence of skin irritation was noted during the study.

Other effects:

/

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material produced a primary irritation index of 1.0 and was classified as a MILD IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
The test material did not meet the criteria for classification as irritant or corrosive according to the EU labelling regulations Commission Directive 2001/59/EC.

Executive summary:

Introduction. The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

• OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted 24 April 2002)
• Commission Directive 92/69/EEC Method B4 Acute Toxicity (Skin Irritation)
• United States Environmental Protection Agency Health Effects Test Guidelines OPPTS 870.2500 Acute Dermal Irritation August 1998 Results. A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight erythema and very slight oedema. Two treated skin sites appeared normal at the 48-hour observation and one treated skin site appeared normal at the 72-hour observation. No corrosive effects were noted. 3-minute and 1-hour semi-occluded applications of the test material to the intact skin of one rabbit produced no evidence of skin irritation. Conclusion. The test material produced a primary irritation index of 1.0 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. The test material did not meet the criteria for classification as irritant or corrosive according to the EU labelling regulations Commission Directive 2001/59/EC.

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:

29/10/2001-12/11/2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP comparable to OECD guideline

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

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

Principles of method if other than guideline:

/

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: 6 weeks
- Weight at study initiation: 1-3.5 kg
- Housing: individually in labelled cages with perforated floors.
- Diet (e.g. ad libitum): +/- 100g per day / hay twice a week
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):21 +/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12hrs dark/12hrs light

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 96.7 (95.6-98.6) mg

Duration of treatment / exposure:

24hours

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with 2% fluorescein in water + to remove residual test substance, rinsed with approximately 50ml tepid water
- Time after start of exposure: 24 hours

SCORING SYSTEM:Corneal irritation (Opacity: degree of density): 0-4
Iridic irritation: 0-2, Conjunctival irritation: Redness: 0-3, Chemosis: 0-4, Discharge: 0-3

TOOL USED TO ASSESS SCORE: standard lighting or an ophthalmic examination lamp.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean 24-72 hours

Score:

0.3

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: mean 24-72 hours

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: mean 24-72 hours

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: mean 24-72 hours

Score:

0

Max. score:

2

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: mean 24-72 hours

Score:

0

Max. score:

2

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: mean 24-72 hours

Score:

0

Max. score:

2

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean 24-72 hours

Score:

2.3

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: mean 24-72 hours

Score:

2

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean 24-72 hours

Score:

0.7

Max. score:

3

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean 24-72 hours

Score:

1

Max. score:

4

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean 24-72 hours

Score:

0.3

Max. score:

4

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: mean 24-72 hours

Score:

0

Max. score:

4

Reversibility:

not specified

Irritant / corrosive response data:

In one animal, corneal injury was seen as opacity (maximum grade 1) and epithelial damage (max. 5% of the corneal area). The opacity had resolved within 48 hours and the epithelial damage within 72 hours.
Irritation of the conjunctivae was seen as redness, chemosis and discharge, which had completely resolved within 7 days in all animals.
No irridial irritation was observed.

Other effects:

Corrosion, colouration, toxicity/mortality: no

Interpretation of results:

Category 2A (irritating to eyes)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelins in Commision Directive 93/21/EEC), FR-1025M does not have to be classified and has no obligatory labelling requirement for eye irritation.
However according to CLP-Regulation (EC) No 1272/2008, FR-1025%M is classified as Irritating to eyes (Category 2) as at least in 2 of 3 tested animals, a positive response of conjunctival redness >=2.

Executive summary:

The study was carried out based on the guidelines described in: EC B5 and OECD 405.

Single samples of approximately 97 mg of FR-1025M were instilled into one eye of each of three rabbits. Two animals were examined 1, 24, 48 and 72 hours and 7 days after instillation. In addition, one animal was examined 1, 24, 48 and 72 hours and 7 days after instillation.

Instillation of the test substance resulted in effects on the cornea, iris and conjunctivae. In one animal, corneal injury was seen as opacity (max grade 1) and epithelial damage (max 5% of the corneal area). The opacity had resolved within 48 hours and the epithelial damage within 72 hours.

Irritation of the conjunctivae was seen as redness, chemosis and discharge, which had completely resolved within 7 days in all animals.

Remnants of the test substance were present in the eyes of all animals on day 1 and/or day 2.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (93/21/EEC), FR-1025M does not have to be classified and has no obligatory labelling requirement for eye irritation.

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Most recent study

Justification for selection of eye irritation endpoint:
Most recent study

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelins in Commision Directive 93/21/EEC), FR-1025M does not have to be classified and has no obligatory labelling requirement for eye irritation. However according to CLP-Regulation (EC) No 1272/2008, FR-1025%M is classified as Irritating to eyes (Category 2) as at least in 2 of 3 tested animals, a positive response of conjunctival redness >=2.