Registration Dossier

Administrative data

Description of key information

Skin, rabbit (OECD 404): not irritating

Eye, rabbit (OECD 405): 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:
09 - 25 Dec 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted Apr 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
The Department of Health of the Government of the United Kingdom, UK
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Belton, UK
- Age at study initiation: 12 - 20 weeks old
- Weight at study initiation: 2.06 - 2.27 kg
- Housing: animals were individually housed in suspended cages, with environmental enrichment
- Diet: 2030 Teklad Global Rabbit diet (Harlan Teklad, Bicester, UK), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
other: not required, untreated sites of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
72 h
Reading time points: 0, 1, 24, 48 and 72 h
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: approximately 6 cm² on the dorsal/flank area
- Type of wrap if used: the test area was covered with a gauze patch (2.5 cm x 2.5 cm) that was secured in place with a strip of surgical adhesive tape, and an elasticated corset was wrapped around the trunk of the animal

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substance was removed from the test site by gentle swabbing with cotton wool soaked in water
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: mean after 24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: mean after 24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
The erythema and edema scores for 3/3 animals were 0 at all reading time points. No skin irritation effects were noted in any animal at any reading time point.
Other effects:
No adverse effects on body weight was noted.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: not classified
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 Dec 2009 - 14 Jan 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted Apr 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
The Department of Health of the Government of the United Kingdom, UK
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Belton, UK
- Age at study initiation: 12 - 20 weeks old
- Weight at study initiation: 2.36 - 2.94 kg
- Housing: animals were individually housed in suspended cages, with environmental enrichment
- Diet: 2030 Teklad Global Rabbit diet (Harlan Teklad, Bicester, UK), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (approximately 88 mg)
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 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the eye was not washed after test substance administration

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: opthalmoscope
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: mean after 24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: mean after 24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: mean after 24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: mean after 24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
3/3 animals had moderate conjunctivae and chemosis (score 2) at the 1-hour reading time point. At the 24-hour reading time point the conjunctivae and chemosis readings in 3/3 rabbits had reduced in severity (score 1), and all eye irritation effects had cleared within 48 hours after test substance administration. No animals showed any irritation effects on the cornea and iris at any reading time point.
Other effects:
No adverse effects on body weight were reported.

Table 1: individual eye irritation scores

 

Rabbit #

 

Time

 

conjunctivae

 

iris

 

cornea

 

redness

chemosis

1

 

 

 

 

1 h

2

2

0

0

24 h

1

1

0

0

48 h

0

0

0

0

72 h

0

0

0

0

Average*

0.33

0.33

0.0

0.0

2

 

 

 

 

1 h

2

2

0

0

24 h

1

1

0

0

48 h

0

0

0

0

72 h

0

0

0

0

Average*

0.33

0.33

0.0

0.0

3

 

 

 

 

1 h

2

2

0

0

24 h

1

1

0

0

48 h

0

0

0

0

72 h

0

0

0

0

Average*

0.33

0.33

0.0

0.0

* mean of 24 + 48 + 72 h

 

 

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

A skin irritation study was performed with Reaction mass of 1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene] and 1,3-dibromo-2-(2,3-dibromo-2-methylpropoxy)-5-{2-[3,5-dibromo-4-(2,3,3-tribromo-2-methylpropoxy)phenyl]propan-2-yl}benzene, according to OECD guideline 404 and under GLP conditions (Sanders, 2010). 0.5 g of the test substance moistened with 0.5 mL water was applied to the clipped skin of 3 male New Zealand White rabbits and held in place by a semi-occlusive dressing for 4 hours. The skin irritation effects were scored 0, 1, 24, 48 and 72 hours after patch removal. No erythema or edema was observed in any animal at any time point. The mean erythema and edema scores (over 24, 48 and 72 hours) were 0, 0 and 0, for each animal, respectively. Based on the results of the conducted study, the test substance is not considered to be irritating to the skin.

 

Eye irritation

The potential eye irritating effect of Reaction mass of 1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene] and 1,3-dibromo-2-(2,3-dibromo-2-methylpropoxy)-5-{2-[3,5-dibromo-4-(2,3,3-tribromo-2-methylpropoxy)phenyl]propan-2-yl}benzene was assessed in an eye irritation study performed according to OECD guideline 405 and under GLP conditions (Sanders, 2010). 0.1 mL of the test substance was instilled into one eye of 3 male New Zealand White rabbits. The eye irritation effects were scored 1, 24, 48 and 72 hours after instillation. 3/3 animals had moderate conjunctivae and chemosis (score 2) at the 1-hour reading time point. At the 24-hour reading time point the conjunctivae and chemosis readings were less severe (score 1), and all eye irritation effects had cleared within 48 hours after test substance administration. No animals showed any irritation effects on the cornea and iris at any reading time point. The mean conjunctivae score (over 24, 48 and 72 hours) was 0.33 for all 3 animals. The mean chemosis score (over 24, 48 and 72 hours) was 0.33 for all 3 animals. Based on the results of the study, the test substance is not considered to be irritating to the eyes.

Justification for classification or non-classification

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