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

Endpoint summary

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

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted Apr 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

The Department of Health of the Government of the United Kingdom, UK

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted Apr 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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.