Registration Dossier

Administrative data

Description of key information

In an acute dermal irritation/corrosion study acc. OECD 404 with4-(Methacryloyloxy) benzophenone by single dermal application to rabbits at a dose of 0.5 g showed neither irritant nor corrosive effects.

Neither mortalities nor significant clinical signs of toxicity were observed.

In an eye irritation/corrosion study with 4-(Methacryloyloxy)benzophenone acc. OECD 405,single ocular instillation of the test item 4-(Methacryloyloxy)benzophenone to rabbits at a dose of 0.1 g produced slight irritant effects, which were fully reversible within 48 hours in all animals.Neither mortalities nor significant clinical signs of toxicity were observed.

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:
22.10.2009 to 02.12.2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
4-(Methacryloyloxy) bezophenone 97.26 %
Benzophenone acetate: 1.95 %
Species:
rabbit
Strain:
New Zealand White
Remarks:
Healthy New Zealand White Rabbits, Crl: KBL (NZW)
Details on test animals and environmental conditions:
Test System
Species/strain: Healthy New Zealand White Rabbits, Crl: KBL (NZW)
Source: Charles River Deutschland, D-97633 Sulzfeld
Sex: female
Body weight at the beginning of the study:> 2 kg
Age at the beginning of the study: approximately 15 weeks old
Number of animals: 3
The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to Art. 9.2, No.7 of the German Act on Animal Welfare the animals were bred for experimental purposes.

Housing and Feeding Conditions
Semi barrier in an air-conditioned room
Temperature: 18 ± 3°C (recommendations ofTVT, GV-SOLAS
Relative humidity: 55 ± 10%
Artificial light, sequence being 12 hours light, 12 hours dark
Air change: at least I 0 x / hour
Free access to autoclaved hay and toAltromin 2123 maintenance diet for rabbits (lot no. 1411 ), rich in crude fibre
Free access to tap water (drinking water, municipal residue control, microbial. controlled periodically)
Housed in ABS -plastic rabbit cages, floor 4200 cm2
Adequate acclimatisation period (at least 5 days)
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
other: The untreated right side served as control.
Amount / concentration applied:
0.5 g per test site
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, 72 hours
Number of animals:
3
Details on study design:
Preparation of the Animals:
Approximately 24.5 hours before the test, the fur was removed from the dorsal area of the trunk by using an electric clipper. Care was taken to avoid abrading the skin, and only animals with healthy intact skin were used.

Initial Test (in vivo Dermal Irritation/Corrosion Test using one Animal):
The test item was not expected to produce corrosion but might be irritating. Therefore, a single patch was applied to one animal for 4 hours.

Application:
The test item was applied first to a gauze patch at a single dose. To ensure good skin contact, it was moistened with aqua ad injectionem (B. Braun Melsungen, lot no. 7494Al91, expiry date: 1112010). The patch was then applied to the skin on a small area ( approx. 6 cm2 ) on the left side of the dorsal area. The gauze was held in place with non-irritating tape. The untreated right side served as control. The patch was fixed with a semi-occlusive dressing. The limits of the application site were marked with an ink marker.

Dose Level:
A dose of 0.5 g of the test item was applied to each test site.

Exposure Period:
The test item was held in contact with the skin throughout a 4-hour period. At the end of the exposure period the residual test item was removed by using aqua ad injectionem.

Confirmatory Test:
The results of the initial test did not indicate the test item to be corrosive or a severe irritant to the skin using the procedure described. In order to confirm the response,
two additional animals were treated in the same manner.

Observation Period:
All animals were observed for 72 hours after the patch removal.

Clinical Observation
For the determination of classification-relevant values, the animals were examined for signs of erythema and oedema at 1 hour as well as 24, 48 and 72 hours after patch removal. Dermal irritation was scored and recorded according to the grades inthe table below. Any other signs such as hyperplasia, scaling,
discoloration, fissures and scabs or any systemic effects were also recorded. For the initial test in one animal, the test site was also examined immediately after the patch has been removed.

Irritation parameter:
erythema score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Other effects:
There were no significant body weight changes during the contact and observation period

  Dermal irritation evaluation:

 

 

 Irritation (hours after patch removal)

Animal No.

Appl. site

1 hour

24 hours

48 hours

72 hours

 

 

erythema

oedema

erythema

oedema

erythema

oedema

erythema

oedema

1

Test item

0

0

0

0

0

0

0

0

control

0

0

0

0

0

0

0

0

2

Test item

0

0

0

0

0

0

0

0

control

0

0

0

0

0

0

0

0

3

Test item

0

0

0

0

0

0

0

0

control

0

0

0

0

0

0

0

0

 

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study, single dermal application of the test item 4-(Methacryloyloxy)benzophenone to rabbits at a dose of 0.5 g showed neither irritant nor corrosive effects.
Neither mortalities nor significant clinical signs of toxicity were observed.
In conformity with the EC criteria for classification and labelling requirements for dangerous substances and preparations according to Annex VI of Commission Directive 2001/59/EC and Annex I of Regulation (EC) 1272/2008, the test item 4-(Methacryloyloxy)benzophenone does not have to be classified and has no obligatory labelling requirement for skin irritation.
Executive summary:

In an acute dermal irritation/corrosion study acc. OECD 404 with 4-(Methacryloyloxy) benzophenone by single dermal application to rabbits at a dose of 0.5 g showed neither irritant nor corrosive effects.

Neither mortalities nor significant clinical signs of toxicity were observed.

In conformity with the EC criteria for classification and labelling requirements for dangerous substances and preparations according to Annex VI of commission Directive 2001/59/EC and Annex I of Regulation (EC) 1272/2008, the test item

4-(Methacryloyloxy)benzophenone does not have to be classified and has no obligatory labelling requirement for skin irritation.

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:
22.10.2009 to 04.01.2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
4-(Methacryloyloxy) bezophenone 97.3 %
Benzophenone acetate: 1.95 %
Species:
rabbit
Strain:
New Zealand White
Remarks:
Healthy New Zealand White Rabbits, Crl: KBL (NZW)
Details on test animals or tissues and environmental conditions:
Sex: female
Body weight at the beginning of the study: > 2 kg
Age at the beginning of the study: approximately 18 weeks old
Number of animals: 3
The animals were derived from a controlled full barrier maintained breeding system
(SPF). According to Art. 9.2, No.7 of the German Act on Animal Welfare the animals were bred for experimental purposes.

Housing and Feeding Conditions
Semi-barrier in an air-conditioned room Temperature: 18 ± 3°C (recommendations ofTVT, GV-SOLAS;
Relative humidity: 55± 10%
Artificial light, sequence being 12 hours light, 12 hours dark
Air change: at least 10 x / hour
Free access to autoclaved hay and to Altromin 2123 maintenance diet for rabbits (lot no. 1411 ), rich in crude fibre
Free access to tap water (drinking water, municipal residue control, microbial.controlled periodically)
Housed in ABS - plastic rabbit cages, floor 4200 cm2
Adequate acclimatisation period (at least 5 days)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0,1 g per test site.
The test item was ground to a fine dust using a mortar and pestle. It was applied directly.
Observation period (in vivo):
The animals were observed for 72 hours after dosing.
Number of animals or in vitro replicates:
3
Details on study design:
Application
The test item was applied at a single dose in the conjunctival sac of one eye of each test animal after pulling the lower lid away from the eyeball. The lids were then gently held together for about 1 second in order to prevent loss of the material. The untreated contralateral eye served as control. Only part of the test item was applied as the full amount did not fit into the eye completely.
Confirmatory Test
The results of the initial test did not indicate the test item to be corrosive or a severe irritant to the eye using the procedure described. In order to confirm the response.
The eyes were not rinsed.

The eyes were examined for signs of irritation throughout the observation period.
For the calculation only the 24, 48 and 72 hour readings were used.
At the end of the observation period the treated eyes were examined with the aid of a fluorescein solution (Fluoreszein SE Thilo®, lot no. H 901, expiry date: 12/2010).
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
The test item produced ilTitant, but no cotTosive ocular effects after instillation into the eyes of3 female rabbits (strain NZW) (Tables 3 to 5).
Neither mortalities nor significant clinical signs of toxicity were observed.
The eyes were not rinsed.
Upon fluorescein examinations at the end of the observation period of 72 h no corneal lesions were found in any animal.
1 h post application, conjunctival discharge grade 2 was observed in animal no. 1, conjunctival discharge grade 1 was observed in animals no. 2 and 3.
Conjunctival redness and chemosis were also observed in animal no. 1, 2 and 3,

Eye irritation scores animal no.1

Animal no. 1

 

Single data

Average score (24, 48 and 72 h)

 

Time post application

 

 

1 hour

24 hour

48 hour

72 hour

 

 

T/C

T/C

T/C

T/C

 

Cornea

0/0

0/0

0/0

0/0

0

Iris

0/0

0/0

0/0

0/0

0

Conjunctival redness

1/0

1/0

0/0

0/0

0.33

Conjunctival chemosis

1/0

0/0

0/0

0/0

0

 

Eye irritation scores animal no.2

Animal no. 2

 

Single data

Average score (24, 48 and 72 h)

 

Time post application

 

 

1 hour

24 hour

48 hour

72 hour

 

 

T/C

T/C

T/C

T/C

 

Cornea

0/0

0/0

0/0

0/0

0

Iris

0/0

0/0

0/0

0/0

0

Conjunctival redness

1/0

1/0

0/0

0/0

0.33

Conjunctival chemosis

1/0

0/0

0/0

0/0

0

 

Eye irritation scores animal no.2

 

Animal no. 3

 

Single data

Average score (24, 48 and 72 h)

 

Time post application

 

 

1 hour

24 hour

48 hour

72 hour

 

 

T/C

T/C

T/C

T/C

 

Cornea

0/0

0/0

0/0

0/0

0

Iris

0/0

0/0

0/0

0/0

0

Conjunctival redness

1/0

1/0

0/0

0/0

0.33

Conjunctival chemosis

1/0

0/0

0/0

0/0

0

 

T=test item, C=control

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study, single ocular instillation of the test item 4-(Methacryloyloxy)benzophenone to rabbits at a dose of 0.1 g produced slight irritant effects, which were fully reversible within 48 hours in all animals.
Neither mortalities nor significant clinical signs of toxicity were observed.
In conformity with the EC criteria for classification and labelling requirements for dangerous substances and preparations according to Annex VI of Commission Directive 2001159/EC and Annex I of Regulation (EC) 1272/2008, the test item 4-(Methacryloyloxy )benzophenone does not have to be classified and has no obligatory labelling requirement for eye irritation
Executive summary:

In an eye irritation/corrosion study with 4-(Methacryloyloxy)benzophenone acc. OECD 405,single ocular instillation of the test item 4-(Methacryloyloxy)benzophenone to rabbits at a dose of 0.1 g produced slight irritant effects, which were fully reversible within 48 hours in all animals. Neither mortalities nor significant clinical signs of toxicity were observed.

In conformity with the EC criteria for classification and labelling requirements for dangerous substances and preparations according to Annex VI of Commission Directive 2001159/EC and Annex I of Regulation (EC) 1272/2008, the test item 4-(Methacryloyloxy )benzophenone does not have to be classified and has no obligatory labelling requirement for eye irritation

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

In conformity with the EC criteria for classification and labelling requirements for dangerous substances and preparations according to Annex VI of commissionDirective 2001/59/EC and Annex I of Regulation (EC) 1272/2008, the test item

4-(Methacryloyloxy)benzophenone does not have to be classified and has no obligatory labelling requirement for skin irritation and eye irritation.