Registration Dossier

Administrative data

Description of key information

Skin irritation: not irritating; two studies according to US FHSA Federal regulation: 16 CFR 1500.41; GLP / pre-GLP; one study according to OECD guideline 402; GLP
Eye irritation: not irritating; similar to OECD guideline 405; GLP

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2011-10-19 to 2011-12-27
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Dermal irritation data recorded in the context of an acute dermal toxicity study with 2000 mg/kg bw. GLP.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
other: EU Method B.3 (Acute Toxicity (Dermal), adopted 30 May 2008
Deviations:
yes
Remarks:
3 animals were subject to reduced exposure time ranging between >4 to 24 hours
Qualifier:
according to guideline
Guideline:
other: OECD Guideline 402 (Acute Dermal Toxicity), adopted 24th Feb 1987
Deviations:
yes
Remarks:
3 animals were subject to reduced exposure time ranging between >4 to 24 hours
Principles of method if other than guideline:
Method: acute dermal toxicity test with full assessment of dermal irritation
GLP compliance:
yes (incl. QA statement)
Remarks:
Certificate dated 6 April 2009
Specific details on test material used for the study:
- Name of test material (as cited in study report): Benzyl methacrylate
Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- WISTAR rats Crl:WI(Han) (full barrier)
- Age at study initiation: males: approx. 13 weeks, females: approx. 14 weeks
- Weight at study initiation: males: 250-267 g, females: 205-223 g
- Fasting period before study: no
- Housing: separate IVC cages, type III H, polysulphone cages on Altromin saw figre bedding, full barrier in air-conditioned room
- Diet (e.g. ad libitum): Altromin 1324 maintenance diet for rats and mice, ad libitum
- Water (e.g. ad libitum): tap water, sulphur acidified to a pH value of approx. 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 10/hr
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 2011-09-20 to 2011-11-10
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): n/a (undiluted)
Duration of treatment / exposure:
24 h (except for 3 test animals which unwrapped themselves overnight, leading to a shortened application period of 4 to 24 hours)
For the animals which unwrapped themselves, no signs of toxicity and significant dermal irritation were observed. As at the 4 h control observation the dressing was tight on all animals, it is very likely that the 3 animals unwrapped themselves clearly after the 4 h period. It can be expected that these animals have been exposed to the test item partially also by the oral route, while grooving, in addition to the dermal route.
As the normal exposure time in skin irrrittation studies according to the international guidelines does not exceed 4 hours, it is concluded that the abbreviated exposure period has no effect on the overall result and the classification of the test item, and that a sufficient estimation of the dermal irritation is ensured.
The validity of the study is not affected and according to animal welfare reasons it was decided not to repeat the study.
Observation period:
14 d
Number of animals:
5 per sex
Details on study design:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10
- Type of wrap if used: gauze-dressing with non-irritating tape, fixed with additional dressing in suitable manner.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): tap water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): n/a (undiluted)
- Constant volume or concentration used: yes (single dose)

OBSERVATIONS
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observation several times on day of dosing (at least once during first 30 minutes and with special attention given during the first 4 hours post-dose). Symptoms were recorded as soon as noticed. Thereafter, daily observations for clinical signs until end of observation period. All abnormalities were recorded. Animals were weighed on day 1 (prior to application of dose) and on day 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed:
-- In case of gross pathological changes, tissues were preserved for a possible histopathological evaluation.
-- The treated areas of skin were examined daily for signs of primary skin irritation. Signs of erythema and oedema were assessed using the scoring system laid down in OECD Guideline 404, adopted 24th April 2002.
Irritation parameter:
erythema score
Remarks:
mean
Basis:
animal #2
Remarks:
female
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 8 d
Irritation parameter:
erythema score
Remarks:
mean
Basis:
animal: #1, #3, #4, #5 female
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
mean
Basis:
animal: males 1-5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
mean
Basis:
animal: females 1-5, males 1-5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Other effects:
this study is described in detail in section 8.5.3 “Acute toxicity: dermal”

- very slight erythema (grade 1, reversible within 8 days) was observed in 1/5 females on days 4, 5, and 7; this animal showed also eschar (up to day 10) and desquamation (up to day 12)
- eschar, desquamation and scratches were observed in one further female, without leading to scoring
- all effects were reversible within 13 days
- females with reduced exposure time due to unwrapping showed either no effects or only non-scored eschar (day 5 to 7) or scratches (day 7)
- No skin irritation was observed at the males.

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
In this acute dermal toxicity study in rat BNMA was found to be not irritating to the skin at a dose of 2000 mg/kg bw.
Executive summary:

In an acute dermal toxicity study according to OECD guideline 402 (24 Feb 1987), 5 female and 5 male Wistar rats were dermally exposed to BNMA at a concentration of 2000 mg/kg bw for 24 h to 10% body surface area. The test substance was removed by washing with tap water after 24 h.

Animals were observed for 14 days. Irritation was scored by the method given in OECD guideline 404 (24th April 2002).

In 1/5 females very slight erythema was observed, which was fully reversible within 8 days. All other animals showed no signs of dermal irritation.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
April 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
Test procedure according to national (US) standard, substantial deviations to international guidelines regarding integrity of treated skin, type of dressing, exposure duration and length of recovery period. Pre-GLP.
Qualifier:
according to guideline
Guideline:
other: US FHSA Federal regulation: 16 CFR 1500.41
GLP compliance:
no
Remarks:
Pre-GLP.
Specific details on test material used for the study:
- Name of test material (as cited in study report): Benzyl methacrylate
Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Type of coverage:
occlusive
Preparation of test site:
other: left side: intact; right side: abraded
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

VEHICLE
no data
Duration of treatment / exposure:
24 h
Observation period:
72 h (evaluation after 24 and 72 h)
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 1 sqareinch
- % coverage: no data
- Type of wrap if used: adhesive tape + wrapped with an impervious material
- The test item was applied to the intact and abraded test sites of each individual rabbit.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data

SCORING SYSTEM:
According to US Federal Hazardous Substances Control Act, 16 CFR 1500.41.similar to OECD guideline 404 (adopted 24th April 2002)
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean 24 + 72 h
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: occlusive, 24 h exposure, observation time 72 h, shaved intact skin, mean 24 + 72 h, 48 h was not evaluated/scored.
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean 24 + 72 h
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: occlusive, 24 h exposure, observation time 72 h, shaved intact skin, mean 24 + 72 h, 48 h was not evaluated.
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean 24 + 72 h
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: occlusive, 24 h exposure, observation time 72 h, shaved intact skin, mean 24 + 72 h, 48 h was not evaluated. Study termination at 72 h, thus, reversibility cannot be evaluated
Irritation parameter:
erythema score
Basis:
animal: #4, #5, #6
Remarks:
mean 24 + 72 h
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: occlusive, 24 h exposure, observation time 72 h, shaved intact skin, mean 24 + 72 h, 48 h was not evaluated.
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean 24 + 72 h
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: occlusive, 24 h exposure, observation time 72 h, shaved intact skin, mean 24 + 72 h, 48 h was not evaluated.
Irritation parameter:
edema score
Basis:
animal: #2, #3
Remarks:
mean 24 + 72 h
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: intact skin, no scoring at 48 h
Irritation parameter:
edema score
Basis:
animal: #4, #5, #6
Remarks:
mean 24 + 72 h
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: occlusive, 24 h exposure, observation time 72 h, shaved intact skin, mean 24 + 72 h, 48 h was not evaluated.
Irritant / corrosive response data:
Intact skin:
24 h after application of the test item at 1/6 treated sites a well-defined erythema (score 2) and a slight edema (score 2, edges of area well-defined by definite raising ), at 2/6 treated sites a very slight erythema (score 1, barely perceptile) and a very slight edema (score 1, barely perceptible) were observed. These effects were fully reversible at the 72 h scoring except of one animal which still showed a erythema score 1.
3/6 treated intact sites showed no skin reactions at all.
The observation time did not extend beyond 72 hours, even though a slight skin response was still present at that time in one animal. Therefore, the full reversibility of the effects can not be proved. However skin effects showed clear tendency of reversibility. At study termination, reversibility was complete in 2/3 affected animals and almost complete in the remaining 1/3 affected animal. Therefore, a full reversibiity in all animals seems to be very likely if the observation period had been extended to the period stipulated in the international guidelines.

The treated abraded skin sites showed identical effects as the intact sites.

- After 72 h only in one animal very slight erythema was observed. No details on reversibility are available as no further examination of the animals was conducted after that timepoint.

rabbit number

reaction

24 h

72 h

left - intact

right - abraded

left - intact

right - abraded

1

erythema

2

2

0

0

edema

2

2

0

0

2

erythema

1

1

0

0

edema

1

1

0

0

3

erythema

1

1

1

1

edema

1

1

0

0

4

erythema

0

0

0

0

edema

0

0

0

0

5

erythema

0

0

0

0

edema

0

0

0

0

6

erythema

0

0

0

0

edema

0

0

0

0

Interpretation of results:
slightly irritating
Conclusions:
In a primary dermal irritation study according to US FHSA Federal regulation: 16 CFR 1500.41, only slight primary skin reactions were observed which were completely reversible or showed a clear tendency to reversibility within the observation period of just 72 h. Considering that the US guideline stipulates a much more intensive exposure regime in comparison to the relevant recent EU and OECD guidelines, the substance showed only slight irritating activity in this study.
Executive summary:

In a primary dermal irritation study according to US FHSA Federal regulation: 16 CFR 1500.41, 6 rabbits were dermally exposed to 0.5 mL of BNMA to approximately 6.25 cm² body surface area. Two application sites per animal were treated, one site was left intact, the other was abraded. Test sites were covered with an occlusive dressing for 24 hours. Animals were observed for 72 hours. Irritation was scored according to FHSA Federal guideline 16 CFR 1500.41. This scoring system is similar to OECD guideline 404.

24 h after application of the test item at 1/6 treated intact sites a well-defined erythema (score 2) and a slight edema (score 2, edges of area well-defined by definite raising ), at 2/6 treated intact sites a very slight erythema (score 1, barely perceptile) and a very slight edema (score 1, barely perceptible) were observed. These effects were fully reversible at the 72 h scoring except of one animal which still showed a erythema score 1.

3/6 treated intact sites showed no skin reactions at all.

The observation time did not extend beyond 72 hours, even though a slight skin response was still present at that time in one animal. Therefore, the full reversibility of the effects can not be proved. However skin effects showed clear tendency of reversibility. At study termination, reversibility was complete in 2/3 affected animals and almost complete in the remaining 1/3 affected animal. Therefore, a full reversibiity in all animals seems to be very likely when the observation period had been extended to the period stipulated in the international guidelines.

The treated abraded skin sites showed identical effects as the intact sites.

In this test, the test substance showed only a slight irritating activity.

Study performance does not comply with requirements of the relevant recent EU and OECD guidelines, were semi-occlusive dressing, an exposure period of 4 hours, treatment of only intact skin and a recovery period of up to 14 days is stipulated. Study is therefore of limited adequacy for C&L purposes due to intensity of the exposure regime and too short recovery period.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1984-04-05 to 1984-04-08
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
Test procedure according to national (French) standard, substantial deviations to international guidelines regarding integrity of treated skin, type of dressing, exposure duration and length of recovery period. GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
other: US FHSA Federal regulation: 16 CFR 1500.41
Qualifier:
according to guideline
Guideline:
other: Journal officiel de la Republique Francaise, 21 Feb 1982
GLP compliance:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): Methacrylate de Benzyle (MABz)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 12 to 16 weeks
- Weight at study initiation: 2.25 to 2.98 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): standard laboratory rabbit diet ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 ± 2.5°C
- Humidity (%): 54 – 58%
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
occlusive
Preparation of test site:
other: left side: intact; right side: abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): pure substance as supplied
Duration of treatment / exposure:
24 h
Observation period:
72 h (evaluation after 24 and 72 h)
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: absorbent lint BPC, polythene, patches were held in position with adhesive strapping (Sleek); to prevent interference with the patches, an elasticated corset was applied
- The test item was applied to the intact and abraded test sites of each individual rabbit.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was removed by gentle swabbing with cotton wool soaked in lukewarm water
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scale, similar to OECD Guideline 404 (adopted 24th April 2002)
Irritation parameter:
erythema score
Basis:
animal: #1, #4, #5, #6
Remarks:
mean 24 h + 72 h
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: intact skin, no scoring at 48 h, study termination at 72 h, thus, reversibility cannot be evaluated
Irritation parameter:
erythema score
Basis:
animal: #2, #3
Remarks:
mean 24 h + 72 h
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: intact skin, no scoring at 48 h, study termination at 72 h, thus, reversibility cannot be evaluated
Irritation parameter:
edema score
Basis:
animal: #1, #2
Remarks:
mean 24 h + 72 h
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: intact skin, no scoring at 48 h
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean 24 h + 72 h
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: intact skin, no scoring at 48 h, study termination at 72 h, thus, reversibility cannot be evaluated
Irritation parameter:
edema score
Basis:
animal: #4, #5
Remarks:
mean 24 h + 72 h
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: intact skin, no scoring at 48 h, study termination at 72 h, thus, reversibility cannot be evaluated
Irritation parameter:
edema score
Basis:
animal #6
Remarks:
mean 24 h + 72 h
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: intact skin, no scoring at 48 h, study termination at 72 h, thus, reversibility cannot be evaluated
Irritant / corrosive response data:
Intact skin:
24 h after application of the test item at 6/6 treated sites a well-defined erythema (score 2) was observed. Slight edema (score 2; edges of area well defined by definite raising) was present in 4/6 animals, very slight edema (score 1; barely perceptible) in 1/6 animals and severe edema (score 4; raised more than 1 mm and extending beyond area of exposure) in 1/6 animals.
After 72 h 2/6 animals still showed well defined erythema (score 2), 4/6 animals showed very slight erythema (score 1; barely perceptible). Slight edema (score 2; edges of area well defined by definite raising) was observed in 1/6 animals, very slight oedema (score 1; barely perceptible) in 3/6 animals and no edema in 2/6 animals.

The treated abraded skin sites showed identical effects as the intact sites, with the exeption of one animal that showed score 1 edema (very slight oedema (barely perceptible)) on the abraded test site and no edema at the intact test site.

rabbit number

reaction

24 h

72 h

 intact

 abraded

 intact

 abraded

1

erythema, eschar

2

2

1

1

edema

2

2

0

0

2

erythema, eschar

2

2

2

2

edema

2

2

0

1

3

erythema, eschar

2

2

2

2

edema

1

1

1

1

4

erythema, eschar

2

2

1

1

edema

2

2

1

1

5

erythema, eschar

2

2

1

1

edema

2

2

1

1

6

erythema, eschar

2

2

1

1

edema

4

4

2

2

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
In a primary dermal irritation study similar to US FHSA Federal regulation: 16 CFR 1500.41, only slight to moderate primary skin reactions were observed which showed a clear tendency to reversibility within the observation period of just 72 h. Considering that the US guideline stipulates a much more intensive exposure regime in comparison to the relevant recent EU and OECD guidelines, the substance showed only slight irritating activity in this study.
Executive summary:

In a primary dermal irritation study according to Journal officiel de la Republique Francaise, 21 Feb 1982 (similar to US FHSA Federal regulation: 16 CFR 1500.41), 6 young adult New Zealand White rabbits were dermally exposed to 0.5 mL of BNMA for 24 hours to 2.5 cm x 2.5 cm body surface area. Animals then were observed for 3 days. Irritation was scored by the Draize method. This scoring system is similar to OECD guideline 404.

24 h after application of the test item at 6/6 treated sites a well-defined erythema (score 2) was observed. Slight edema (score 2; edges of area well defined by definite raising) was present in 4/6 animals, very slight edema (score 1; barely perceptible) in 1/6 animals and severe edema (score 4; raised more than 1 mm and extending beyond area of exposure) in 1/6 animals.

After 72 h 2/6 animals still showed well defined erythema (score 2), 4/6 animals showed very slight erythema (score 1; barely perceptible). Slight edema (score 2; edges of area well defined by definite raising) was observed in 1/6 animals, very slight oedema (score 1; barely perceptible) in 3/6 animals and no edema in 2/6 animals.

The treated abraded skin sites showed identical effects as the intact sites, with the exeption of one animal that showed score 1 edema (very slight oedema (barely perceptible)) on the abraded test site and no edema at the intact test site.

The observation time did not extend beyond 72 hours, even though a slight skin response was still present at that time in 6/6 animals. Therefore, the full reversibility of the effects can not be proved. However skin effects showed a tendency of reversibility.

Therefore, a full reversibility in all animals seems to be likely if the observation period had been extended to the period stipulated in the international guidelines.

In this test, the test substance showed a slight irritating activity.

Study performance does not comply with requirements of the relevant recent EU and OECD guidelines, were semi-occlusive dressing, an exposure period of 4 hours, treatment of only intact skin and a recovery period of up to 14 days is stipulated. Study is therefore of limited adequacy for C&L purposes due to intensity of the exposure regime and too short recovery period.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

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:
1984-04-16 to 1984-05-03
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 24th April 2002
Qualifier:
according to guideline
Guideline:
other: Journal Officiel de la Republique Francaise 21 April 1971 and 5 June 1973
GLP compliance:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): Methacrylate de Benzyle (MABz)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: 12 – 16 weeks
- Weight at study initiation: 2.27 – 2.86 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): standard laboratory rabbit diet, ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 ± 4.5°C
- Humidity (%): 50-60%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12


Vehicle:
unchanged (no vehicle)
Controls:
other: untreated contralateral eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): undiluted
Duration of treatment / exposure:
eyes were not rinsed after application
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6 (sex not given)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize, similar to OECD guideline 405 (adopted 24th April 2002)

TOOL USED TO ASSESS SCORE: standard ophthalmoscope (Keeler)
Irritation parameter:
cornea opacity score
Remarks:
mean
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Remarks:
mean
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
mean
Basis:
animal: #2, #4, #6
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.667
Max. score:
3
Reversibility:
fully reversible within: 3 d
Irritation parameter:
conjunctivae score
Remarks:
mean
Basis:
animal: #3, #5
Time point:
24/48/72 h
Score:
0.333
Max. score:
3
Reversibility:
fully reversible within: 2 d
Irritation parameter:
chemosis score
Remarks:
mean
Basis:
animal: #2, #3, #4, #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Remarks:
mean
Basis:
animal: #1, #5
Time point:
24/48/72 h
Score:
0.333
Max. score:
4
Reversibility:
fully reversible within: 2 d
Other effects:
small amount of conjunctival discharge was observed in one animal (#5) after 24 h, but not thereafter
Interpretation of results:
GHS criteria not met
Conclusions:
BNMA is not irritating to the rabbit eye.
Executive summary:

In a primary eye irritation study similar to OECD guideline 405 (adopted 24th April 2002), 0.1 mL of BNMA (purity: 99 - 99.4%, according to supplier) was instilled into the conjunctival sac of 6 young adult New Zealand White rabbits (sex not given) without washing. Animals then were observed for 7 days.  Irritation was scored by the method of Draize.

 

No effects were observed in cornea and iris. Only minimal (grade 1) chemosis and redness were observed in 2 and 3 animals, respectively. All effects were reversible within 72 h.

 

In this study, BNMA is not irritant to the rabbit eye.

GHS criteria not met.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Reliable (RL= 2), relevant and adequate data are available for the skin and eye irritation potential of BNMA.

Skin irritation

Two studies on skin irritation potential of BNMA are available which were conducted according to US FHSA Federal regulation: 16 CFR 1500.41.

 

In a primary dermal irritation study according to US FHSA Federal regulation: 16 CFR 1500.41, 6 rabbits were dermally exposed to 0.5 mL of BNMA to approximately 6.25 cm² body surface area. Two application sites per animal were treated, one site was left intact, the other was abraded. Test sites were covered with an occlusive dressing for 24 hours. Animals were observed for 72 hours. Irritation was scored according to FHSA Federal guideline 16 CFR 1500.41. This scoring system is similar to OECD guideline 404.

24 h after application of the test item at 1/6 treated intact sites a well-defined erythema (score 2) and a slight edema (score 2, edges of area well-defined by definite raising), at 2/6 treated intact sites a very slight erythema (score 1, barely perceptile) and a very slight edema (score 1, barely perceptible) were observed. These effects were fully reversible at the 72 h scoring except of one animal which still showed a erythema score 1.

3/6 treated intact sites showed no skin reactions at all.

The observation time did not extend beyond 72 hours, even though a slight skin response was still present at that time in one animal. Therefore, the full reversibility of the effects can not be proved. However skin effects showed clear tendency of reversibility. At study termination, reversibility was complete in 2/3 affected animals and almost complete in the remaining 1/3 affected animal. Therefore, a full reversibility in all animals seems to be very likely when the observation period had been extended to the period stipulated in the international guidelines.

The treated abraded skin sites showed identical effects as the intact sites.

In this test, the test substance showed only a slight irritating activity.

 

In a primary dermal irritation study according to Journal officiel de la Republique Francaise, 21 Feb 1982 (similar to US FHSA Federal regulation: 16 CFR 1500.41), 6 young adult New Zealand White rabbits were dermally exposed to 0.5 mL of BNMA for 24 hours to 2.5 cm x 2.5 cm body surface area. Animals then were observed for 3 days. Irritation was scored by the Draize method. This scoring system is similar to OECD guideline 404.

24 h after application of the test item at 6/6 treated sites a well-defined erythema (score 2) was observed. Slight edema (score 2; edges of area well defined by definite raising) was present in 4/6 animals, very slight edema (score 1; barely perceptible) in 1/6 animals and severe edema (score 4; raised more than 1 mm and extending beyond area of exposure) in 1/6 animals.

After 72 h 2/6 animals still showed well defined erythema (score 2), 4/6 animals showed very slight erythema (score 1; barely perceptible). Slight edema (score 2; edges of area well defined by definite raising) was observed in 1/6 animals, very slight oedema (score 1; barely perceptible) in 3/6 animals and no edema in 2/6 animals.

The treated abraded skin sites showed identical effects as the intact sites, with the exeption of one animal that showed score 1 edema (very slight oedema (barely perceptible)) on the abraded test site and no edema at the intact test site.

The observation time did not extend beyond 72 hours, even though a slight skin response was still present at that time in 6/6 animals. Therefore, the full reversibility of the effects can not be proved. However skin effects showed a tendency of reversibility.

Therefore, a full reversibility in all animals seems to be likely if the observation period had been extended to the period stipulated in the international guidelines.

In this test, the test substance showed a slight irritating activity.

 

Study performance of both studies does not comply with requirements of the relevant recent EU and OECD guidelines, were semi-occlusive dressing, an exposure period of 4 hours, treatment of only intact skin and a recovery period of up to 14 days is stipulated. Both studies are therefore of limited adequacy for C&L purposes due to intensity of the exposure regime and too short recovery period.

However, the tendency of reversibility can be further proved by the results of an acute dermal toxicity study:

In an acute dermal toxicity study according to OECD guideline 402 (24 Feb 1987), 5 female and 5 male Wistar rats were dermally exposed to BNMA at a concentration of 2000 mg/kg bw for 24 h to 10% body surface area. The test substance was removed by washing with tap water after 24 h.

Animals were observed for 14 days. Irritation was scored by the method given in OECD guideline 404 (24th April 2002).

In 1/5 females very slight erythema was observed, which was fully reversible within 8 days. All other animals showed no signs of dermal irritation.

 

From the available data it can be concluded that BNMA is not irritating to the skin.

 

Eye irritation

In a primary eye irritation study similar to OECD guideline 405 (adopted 24th April 2002), 0.1 mL of BNMA (no information on purity) was instilled into the conjunctival sac of 6 young adult New Zealand White rabbits (sex not given) without washing. Animals then were observed for 7 days.  Irritation was scored by the method of Draize.

No effects were observed in cornea and iris. Only minimal (grade 1) chemosis and redness were observed in 2 and 3 animals, respectively. All effects were reversible within 72 h.

In this study, BNMA is not irritating to the rabbit eye.

There are no data gaps for the endpoint irritation/corrosion. No human information is available for this endpoint. However, there is no reason to believe that these results would not be applicable to humans.

 


Justification for selection of skin irritation / corrosion endpoint:
No single key study has been selected, instead, all availabe studies have been used in a weight-of-evidence approach.

Justification for selection of eye irritation endpoint:
OECD guideline study, GLP

Justification for classification or non-classification

Based on the available data, BNMA does not need to be classified for eye irritation or skin irritation according to regulation (EC) 1272/2008. Thus, no labelling is required.