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Administrative data

Description of key information

Exposure of intact rabbit skin to 2-butoxyethyl methacrylate for a 4-hour period produced slight-moderate erythma on 2/3 animal but no abnormal body weight changes, toxic symptoms / mortality, or skin discolouration. A primary skin irritation index of 0.7 was calculated for 2-butoxyethyl methacrylate. Although the erythema scores were below the threshold for classification, due to the irreversibility of the effects in two animals (desquatmation after 7 days) the substance should be classified as a skin irritant category 2 in accordance with CLP Regulation.

When applied to the eye mucosa of rabbits at 0.1 ml, 2-butoxyethyl methacrylate was found not to produce a significantly irritating reaction, with minimal or no irritating, corrosive, and/or discoloration effects observed for the cornea, iris, or conjunctivae at 24, 48, and 72 hours post-administration. No toxic effects / mortality was exhibited by the test animals. A primary eye irritation index of 0.6 was calculated for 2-butoxyethyl methacrylate and it was determined that classification as a potential eye irritant was not required (CLP Regulation (EC) No. 1272/2008).

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:
July 25, 1984
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:
May 12, 1981
Deviations:
no
Qualifier:
according to
Guideline:
other: Council Directive 79/831/EEC. Annex V, Part B. Methods for the Determination of Toxicity; 4.1.5. Acute Toxicity, 'Skin Irritation'
Deviations:
no
GLP compliance:
yes
Remarks:
(See Bundesanzeiger Nr. 42a, March 2, 1983, FRG)
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Expiration date of the lot/batch: September 1984

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
The test article was applied undiluted
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: New Zealand White rabbits (1 male and 2 female) were obtained from Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf / Switzerland
- Age at study initiation: 12 - 13 weeks at delivery
- Weight at study initiation: 1.7 - 2.2 kg
- Housing: Within individual stainless-steel cages equipped with an automatic cleaning and drinking system (Dipl. Ing. W. Ehret GmbH, Versuchstiertechnik, D 7830 Emmendingen / FRG)
- Diet: Pelleted standard Kliba 341, Batch No. 95/84 rabbit maintenance diet ('Kliba', Klingentalmuehle AG, Switzerland) ad libitum
- Water: Community tap water from Itingen ad libitum
- Acclimation period: Four days under test conditions after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Relative humidity (%): 55 ± 10 %
- Air changes (per hr): Air-conditioned with 10 - 15 air changes / hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light / 12 hours dark and at least 8 hours music/light period
- Other: Hourly monitored environment
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml applied (undiluted) to intact skin of the shaved area
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3 (1 male and 2 female)
Details on study design:
TEST SITE
- Area of exposure: 100 cm2 (10 cm x 10 cm)
- Type of wrap if used: The treated area was covered with a patch of surgical gauze measuring 3.0 cm x 3.0 cm. The gauze was covered with aluminium foil and an occlusive dressing that was wrapped around the abdomen and anchored with an elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: The skin was flushed with Luke warm tap water after removal of the dressing, gauze patch and test material
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
1, 24, 48, and 72 hours post-removal of the surgical gauze dressing and on day 7

SCORING SYSTEM:
- Erythema and eschar formation: Very slight erythema (barely perceptible) - 1; well-defined erythema - 2; moderate to severe erythema - 3; severe erythema (beet redness) to slight eschar formation (injuries in depth) - 4
- Edema formation: Very slight edema (barely perceptible) - 1; slight edema (edges of area well-defined by definite raising) - 2; moderate edema (area raised approximately 1 mm) - 3; severe edema (raised more than 1 mm and extending beyond area of exposure) - 4
- Maximum possible: Erythema and eschar score = 4; edema score = 4; primary irritation score = 8
- Method calculation: The primary irritation index was calculated by totalling the individual cumulative scores and then dividing by the number of figures

OTHER
The nature (and reversibility or otherwise) of any observed corrosion, colouration, body weight change, and toxic symptoms / mortality were described and recorded
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1/24/48/72 h
Score:
0.7
Max. score:
8
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
probability of mild irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
2-Butoxyethyl methacrylate showed a primary skin irritation score of 0.7 when applied to intact rabbit skin. In two animals slight - severe desquamation was observed after 7 days.
Other effects:
No discolouration of the skin was observed that could be related to effects of the test material and the body weight gain of all rabbits was similar. No acute toxic symptoms or mortality occurred during the 7-day test period. Due to the results obtained, no macroscopic organ examination was carried out.

Primary skin irritation score:

Selected observation

Mean score

1 hour

0.0

24 hours

0.7

48 hours

1.3

72 hours

0.7

Mean value of the irritation scores for each type of lesion, calculated for each animal seperately (according to EEC Council Directive 67/548/EEC, April 1983 Brussels, Belgium):

Animal number

Sex Mean 24 - 72 hours
Erythema Edema

114

Male 0.0 0.0

115

Female 0.3 0.0

116

Female 1.3 1.0
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
In a 7-day primary skin irritation study, 4-hour exposure of 2-butoxyethyl methacrylate to intact rabbit skin resulted in an irritation score of 0.7. The the mean grading value for erythema and for edema at 24, 48, and 72 hours was <1.5 (GHS 2011). However, two animals showed signs of desquamation at the end of the testing period (day 7) indicating the substance should be classified as a skin irritant in accrordance with GHS.
Executive summary:

A GLP-compliant primary skin irritation study was carried out for 2-butoxyethyl methacrylate using white New Zealand rabbits of mixed sex. The experiment was performed in line with OECD Guideline 404 (Acute Dermal Irritation / Corrosion) and Council Directive 79/831/EEC. Annex V, Part B. Methods for the Determination of Toxicity; 4.1.5. Acute Toxicity, 'Skin Irritation'. The aim of the study was to establish the irritation potential of 2-butoxyethyl methacrylate to provide a rational basis for risk assessment in humans given that skin contact is a probable route for exposure.

A single 0.5 ml dose of the undiluted substance was applied to an area (10 cm x 10 cm) of shaved rabbit skin following a 4-day acclimation period. The skin was covered with a patch (3.0 cm x 3.0 cm) of surgical gauze that was protected with aluminium foil and an occlusive dressing. After a 4-hour exposure period the dressing was removed, and the skin was flushed with lukewarm tap water. Viability / mortality, corrosive properties of the test article, and skin colour were monitored at 1, 24, 48, and 72 hours and on day 7. Body weight was recorded pre-test and on day 1 and 7. Evaluation of the skin reaction entailed allocating a numerical irritation score to visible erythema and eschar formation and to edema formation in order to grade lesion severity.

No discolouration of the skin was noted that could be related to the test article, although in two rabbits desquamation was observed on day 7. The body weight gain of all rabbits was similar, and no acute toxic symptoms were observed during the test period. Necropsy was not performed due to the results obtained. Totalling the individual cumulative irritation scores and dividing by the number of figures for 1, 24, 48, and 72 hours gave a primary irritation index of 0.7 for 2-butoxyethyl methacrylate. According to the criteria specified in GHS (2011), the registered substance should be classified as irritant to the skin as two if the animals showed signs of inflammation (desquamation) at the end of the test period.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
July 23, 1984
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:
May 12, 1981
Deviations:
no
Qualifier:
according to
Guideline:
other: Council Directive 79/831/EEC. Annex V, Part B. Methods for the Determination of Toxicity; 4.1.6. Acute Toxicity, 'Eye Irritation'
Deviations:
no
GLP compliance:
yes
Remarks:
(See Bundesanzeiger Nr. 42a, March 2, 1983, FRG)
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Expiration date of the lot/batch: September 1984

The test article was applied undiluted.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: New Zealand White rabbits (2 males and 1 female) were obtained from Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf / Switzerland
- Age at study initiation: 12 - 13 weeks at delivery
- Weight at study initiation: 2.3 kg
- Housing: Within individual stainless-steel cages equipped with an automatic cleaning and drinking system (Dipl. Ing. W. Ehret GmbH, Versuchstiertechnik, D 7830 Emmendingen / FRG)
- Diet: Pelleted standard Kliba 341, Batch No. 95/84 rabbit maintenance diet ('Kliba', Klingentalmuehle AG, Switzerland) ad libitum
- Water: Community tap water from Itingen ad libitum
- Acclimation period: Four days under test conditions after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Relative humidity (%): 55 ± 10 %
- Air changes (per hr): Air-conditioned with 10 - 15 air changes / hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light / 12 hours dark and at least 8 hours music/light period
- Other: Hourly monitored environment
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
A single dose of 0.1 ml 2 -n-butoxy-ethylmethacrylate (undiluted) was administered to the conjunctival sac of the left eye in all rabbits and left unwashed
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
The eyes of each animal were examined 1, 24, 48, and 72 hours post-administration
Number of animals or in vitro replicates:
Three rabbits (2 males and 1 female)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM:
Irritation was assessed according to the OECD Guidelines for testing of chemicals, Section 4, No. 405 "Acute eye Irritation / Corrosion" - Adopted May 12, 1981. The corrosive properties of the test article and the colour of the treated eye were described and recorded. The following subjective numerical scoring system was used to grade any eye lesions:

Corneal Irritation
Opacity - degree of density (densest area used for assessment)
- No ulceration or opacity: 0; Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible: 1*; Easily discernible translucent area, details of iris slightly obscured: 2*; Nacrous area, no details of iris visible, size of pupil barely discernible: 3*; Opaque cornea, iris not discernible through the opacity: 4*

Iridic Irritation
- Normal: 0; Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperemia, or injection, any of these or combination thereof, iris still reacting to light (sluggish reaction is positive): 1*; No reaction to light, haemorrhage, gross destruction (any or all of these): 2*

Conjunctival Irritation
Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)
- Blood vessels normal: 0; Some blood vessels definitely hyperemic (injected): 1; Diffuse, crimson colour, individual vessels not easily discernible: 2*; Diffuse beefy red: 3*
Chemosis: lids and/or nictating membranes
- No swelling: 0; Any swelling above normal (includes nictating membranes): 1; Obvious swelling with partial eversion of lids: 2*; Swelling with lids about half closed: 3*; Swelling with lids more than half closed: 4*

Maximum cumulative score: 13
*Starred figures indicate positive effect

TOOL USED TO ASSESS SCORE: Slit-lamp 30 SL (C. Zeiss AG, Zuerich / Switzerland) and a Verta Cliptrix diagnostic-lamp (A. Riegger, Basel / Switzerland)
Irritation parameter:
other: Primary irritation score
Basis:
mean
Time point:
other: 1/24/48/72 h
Score:
0.6
Max. score:
13
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
2-Butoxyethyl methacrylate had a primary irritation score of 0.6 when applied to the rabbit eye mucosa. 1-hour post-administration all animals exhibited symptoms of edema and redness in the conjunctivae, reddened vessels in the sclera, and moderate discharge from the right eye. A reddened conjunctival sac (hardly visible) was observed in one animal after 24 hours, however, past this time point no abnormal changes were visible. No abnormal symptoms were evident in the other two rabbits after 24, 48, and 72 hours. No corrosion of the cornea occurred.
Other effects:
No acute toxic symptoms or mortality was observed in any animal during the test period and the body weight gain of all rabbits was similar. Due to the results obtained no macroscopic organ examination was indicated.

Primary eye irritation score:

Selected observation

Mean score

1 hour

2.0

24 hours

0.3

48 hours

0.0

72 hours

0.0

Mean value of the irritation scores for each type of lesion, calculated for each animal seperately (according to EEC Council Directive 67/548/EEC, April 1983 Brussels, Belgium):

Animal number

Sex Mean 24 - 72 hours

Corneal

opacity

Iris Conjunctivae redness Conjunctivae chemosis

105

Male 0.0 0.0 0.0 0.0

106

Male 0.0 0.0 0.3 0.0

107

Female 0.0 0.0 0.0

0.0

Interpretation of results:
GHS criteria not met
Conclusions:
A primary eye irritation study that involved a single application of 0.1 ml 2-butoxyethyl methacrylate to the left conjunctival eye sacs of three New Zealand rabbits reported a final primary irritation index of 0.6. 2-Butoxyethyl methacrylate did not result in a significantly positive mean grading response with regards to corneal opacity, iritis, conjunctival redness, and/or conjunctival oedema (chemosis) to warrant classification as irritating to the eyes (Category 2) (CLP Regulation (EC) No. 1272/2008).
Executive summary:

To determine the eye irritation potential of 2-butoxyethyl methacrylate, an in vivo experiment was undertaken with New Zealand rabbits of mixed sex that complied with Good Laboratory Practise (GLP). The procedure outlined in the report followed OECD Guideline 405 (Acute Eye Irritation / Corrosion) and Council Directive 79/831/EEC. Annex V, Part B. Methods for the Determination of Toxicity; 4.1.6. Acute Toxicity, 'Eye Irritation'. The aim of the report was to deliver a rational basis for human risk assessment.

A single application of 0.1 2-butoxyethyl methacrylate in undiluted form was administered to the left conjunctival eye sac of three rabbits, which were subsequently left unwashed for the experiment duration. The right eye remained untreated and was used as a reference control. Viability / mortality, corrosive properties of the test article, and eye colouration were monitored and recorded daily, and body weight was recorded pre-test and on day 1 and 7. The eyes were examined for signs of irritation at 1, 24, 48, and 72 hours post-administration. Evaluation of irritation reaction and lesion severity was based on a numerical scoring system the graded corneal irritation (opacity), iridic irritation, and conjunctival irritation (redness and chemosis). The study was terminated 72 hours after article application and all rabbits were killed by intravenous injection of T61.

2-butoxyethyl methacrylate was calculated to produce a primary eye irritation index of 0.6. Conjunctivae redness (hardly visible) was observed in one animal after 24 hours but this was determined not to be related to the substance. The effect was not evident after this point and no additional abnormal change was visible in other animals. The test material did not generate corrosive or toxic symptoms / mortality during the study and due to the overall results obtained, no macroscopic organ examination was indicated. As 2-butoxyethyl methacrylate did not induce a significantly positive response with respect of corneal opacity, iritis, conjunctival redness and/or conjunctival oedema (chemosis) (GHS 2011), the registered substance is concluded not to be an eye irritant. Subsequently, 2-butoxyethyl methacrylate does not require classification according to CLP Regulation (EC) No. 1272/2008.

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

Additional information

As adequate data from the in vivo eye irritation study and in vivo skin irritation/corrosion is available, an in vitro / ex vivo study is not required to fulfil the information requirement for these endpoints.

Justification for classification or non-classification