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Toxicological information

Skin irritation / corrosion

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Administrative data

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

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 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)

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

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
The test article was applied undiluted

Test animals

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

Test system

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

Results and discussion

In vivo

Resultsopen allclose all
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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.