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Toxicological information

Eye irritation

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guidelineopen allclose all
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)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
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.

Test animals / tissue source

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

Test system

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)

Results and discussion

In vivo

Resultsopen allclose all
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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.