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Administrative data

Description of key information

The in vivo skin irritation study with the rabbit revealed no to moderate formation of erythema and no to very slight edema formation, with all effects being fully reversible. In the two in vivo eye irritation studies with the rabbit very slight conjunctivae redness was observed, the effect was fully reversible.  BMBDM therefore is not to be considered as skin irritant or eye irritant.

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:
20/07/1982-23/07/1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline studies with acceptable restrictions.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
: occlusive instead of semi-occlusive dressing, scoring after 4 instead of 1h after application.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Animal Farm of Hoffmann-La Roche at Füllinsdorf, Basel-Land, Switzerland
- Weight at study initiation: greater than 2 kg
- Housing: singly in restrainers during first 6 hours of the test, thereafter in stainless cages
- Diet (e.g. ad libitum): ad libitum (except on the day of administration)
- Water (e.g. ad libitum): tap water ad libitum (except on the day of administration)
- Acclimation period: Minimum of seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 0.5°C
- Humidity (%): 65± 5%
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
abraded
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent vehicle
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 10% in ethanol/2-phenylethanol (50/50) (CAS 60-12-8)

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
exposure time: 4 or 24h
Observation period:
up to 72h after treatment
Number of animals:
Butyl methoxydibenzoylmethane (BMDBM): 6 animals
Vehicle control: 6 animals
Details on study design:
TEST SITE
- Area of exposure: back of the rabbits; left side: abraded skin, right side: intact skin
- coverage: 2x2 cm gauze patch
- Type of wrap if used: occlusive dressing by plastic foil, held in place by elastic network

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 and 24h

SCORING SYSTEM: see Table 1).
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24h
Score:
0.83
Max. score:
4
Reversibility:
other: see Table 2
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24h
Score:
0.17
Max. score:
4
Reversibility:
other: see Table 2
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 48h
Score:
0.5
Max. score:
4
Reversibility:
other: see Table 2
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 48h
Score:
0.17
Max. score:
4
Reversibility:
other: see Table 2
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24h
Score:
1.33
Max. score:
4
Reversibility:
other: see Table 2
Remarks on result:
other: abraded skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24h
Score:
1
Max. score:
4
Reversibility:
other: see Table 2
Remarks on result:
other: abraded skin
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 48h
Score:
1.17
Max. score:
4
Reversibility:
other: see Table 2
Remarks on result:
other: abraded skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 48h
Score:
0.5
Max. score:
4
Reversibility:
other: see Table 2
Remarks on result:
other: abraded skin
Irritant / corrosive response data:
After 4h application of BMDBM (as 10% solution in ethanol/2-phenylethanole 50/50) to intact or abraded rabbit skin, no to well-defined erythema were observed, resulting in a mean score of 0.67 and 1.17 for intact and abraded skin, respectively. Edemas were less pronounced, showing no to very slight response with mean values of 0.11 and 0.83 for intact and abraded skin, respectively.
When testing the solvent solely, the mean irritation scores for erythema formation were 0.56 and 1.00 for intact and abraded skin, respectively. The edema scores were 0.00 and 0.78 for intact and abraded skin, respectively.
These results indicate that the substance tested possesses a slight irritating potential which is mainly caused by the solvent used.

 Table 2: Primary irritation index after 4h exposure of 10% BMDBM in ethanol/2-phenylethanol (50/50) to intact and abraded skin:

Rabbit No.

Erythema score

Edema score

4h

24h

48h

4h

24h

48h

Intact skin

1

0

0

0

0

0

0

2

1

0

0

0

0

0

3

1

2

1

0

0

0

4

0

2

2

0

1

1

5

1

1

0

0

0

0

6

1

0

0

0

0

0

Mean:

0.67

0.83

0.5

0

0.17

0.17

Abraded skin

1

1

1

1

1

1

1

2

1

1

1

1

1

0

3

1

2

1

1

1

1

4

1

2

2

1

1

1

5

1

1

1

1

1

0

6

1

1

1

1

1

0

Mean:

1

1.33

1.17

1

1

0.5

 

 

Table 3: Primary irritation index after 4h exposure of the vehicle (ethanol/2-phenylethanol (50/50)) to intact and abraded skin:

Rabbit No.

Erythema score

Edema score

4h

24h

48h

4h

24h

48h

Intact skin

1

1

1

1

0

0

0

2

1

0

0

0

0

0

3

1

0

0

0

0

0

4

1

1

0

0

0

0

5

1

1

0

0

0

0

6

1

0

0

0

0

0

Mean:

1

0.5

0.17

0

0

0

Abraded skin

1

1

1

1

1

1

1

2

1

1

1

1

1

0

3

1

1

0

1

1

0

4

1

2

1

1

1

1

5

1

1

1

1

1

0

6

1

1

1

1

1

0

Mean:

1

1.17

0.83

1

1

0.33

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Occlusive application of 10% butyl methoxydibenzoylmethane (BMDBM) in ethanol/2-phenylethanol for 4h to intact or abraded rabbit skin caused no to slight erythema and edema. Also the vehicle ethanol/2-phenylethanol (50/50) causes these effects but in a somewhat lower potency.
Executive summary:

After occlusive application of 0.5mL of the test item (10% BMDBM solved in ethanol/2-phenylethanol (50/50)) for 4 hours to intact or abraded rabbit skin, no to moderate formation of erythema and no to very slight edema formation was noted. The mean scores (erythema/edema) were 0.83/0.17 on intact skin and 1.33/1.00 on abraded skin 24h after application. Testing the solvent caused no to very slight erythema and edema resulting in scores (erythema/edema) of 0.50/0.00 on intact skin and 1.17/1.00 on abraded skin 24h after application. It can therefore be concluded that the skin irritations are mainly due to the vehicle used and that BMDBM bears very slight irritating potential.

As the erythema/edema score is <2.3 in all animals no classification as skin irritant according to OECD GHS is needed

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study under GLP with acceptable restrictions in documentation
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
: The test item was dissolved in diethylphtalate, concentration: 5-20%
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Vehicle:
other: diethylphtalate
Controls:
not required
Amount / concentration applied:
0.1 mL of a solution containing 5%, 10% and 20% BMDBM.
Duration of treatment / exposure:
Single application of a 5%, 10% and 20% solution each
Observation period (in vivo):
After 1, 24, 48, and 72h. Post-observation after 7 and 14 days.
Number of animals or in vitro replicates:
Three animals per dose group.
Details on study design:
SCORING SYSTEM: Draize system
Corneal opacity: 0-4
Iris: 0-2
Conjunctival redness: 0-3
Conjunctival swelling (chemosis): 0-4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24-72h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 5% solution
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24-72h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: 5% solution
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24-72h
Score:
0
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: 5% solution
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24-72h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 5% solution
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24-72h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 10% solution
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24-72h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: 10% solution
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24-72h
Score:
0.44
Max. score:
3
Reversibility:
fully reversible within: 2-3d
Remarks on result:
other: 10% solution
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24-72h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 10% solution
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24-72h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 20% solution
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24-72h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: 20% solution
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24-72h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 3d
Remarks on result:
other: 20% solution
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24-72h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 20% solution
Irritant / corrosive response data:
As given above.Single application of a 5-20% solution of BMDBM in diethylphtalate caused weak shortlasting conjuncticval irritation of the rabbit eye. No alteration of the cornea was observed macroscopically.
Other effects:
No further effects were reported
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The 20% solution of butyl methoxydibenzoylmethane (BMDBM) dissolved in diethylphtalate caused weak shortlasting conjunctival irritation of the rabbit eye. No alterations of the cornea was observed macroscopically.
Therefore, BMDBM can be considered as non-irritant to the eye and no classification according to EU CLP is needed.
Executive summary:

The determination of eye irritating effects of butyl methoxydibenzoylmethane (BMDBM) was performed in a study similar to OECD Guideline 405 on three rabbits: BMDBM as 5%, 10%, and 20% solution in diethylphtalate was placed in the conjunctival sac of one rabbit eye and the effects are recorded after 1h, 24h, 48h, 72h, 7 days and 14 days. Observations comprised opacity of the cornea, iris reaction, conjunctival redness and swelling (chemosis).

The instillation of a solution of BMDBM caused concentration-dependent weak conjunctival irritation of the rabbit eye which was fully reversible within up to 3 days. The mean irritation scores for the 20% solution (3 animals, 24 - 72h after administration) were 0 (Cornea opacity), 0 (Iris), 0.67 (Conjunctivae redness), 0 (Chemosis).

Therefore, BMDBM can be considered as non-irritant to the eye and no classification according to EU CLP is needed.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In the study by Kleczak (1982), skin irritation was tested by occlusive application of a 10% BMDBM solution for 4h on intact or abraded rabbit skin. The results revealed no to moderate formation of erythema and no to very slight formation of edema. Testing the solvent caused no to very slight erythema and edema formation.

Therefore, the authors concluded that the irritating potential can mainly be attributed to the solvent used and that BMDBM is at best slightly irritating to skin.

 

Eye irritation:

In two studies by Kleczak (1988 and 1978), eye irritation was tested in the rabbit eye. Both test items, which were a sunscreen cream containing 3% BMDBM and different BMDBM solutions (5-20% BMDBM), caused only very slight conjunctival redness (grade 1 of 4) which was fully reversible within 2-3 days. Therefore, BMDBM can be considered as not irritating to the eyes.


Justification for selection of skin irritation / corrosion endpoint:
Comparable to guideline studies with acceptable restrictions.

Justification for selection of eye irritation endpoint:
Comparable to guideline study under GLP with acceptable restrictions in documentation.

Justification for classification or non-classification

No classification-relevant skin irritating and eye irritating effects were observed in the respective in vivo studies, thus no classification applicable.