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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:
Initiation date: 02-10-'84 Completion date: 16-10- '84
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 guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
4-(1,1-dimethylethyl)cyclohexyl methacrylate
EC Number:
256-277-5
EC Name:
4-(1,1-dimethylethyl)cyclohexyl methacrylate
Cas Number:
46729-07-1
Molecular formula:
C14H24O2
IUPAC Name:
4-(1,1-dimethylethyl)cyclohexyl methacrylate
Specific details on test material used for the study:
Chemical name: t-Butyl cyclohexyl methacrylate
Appearance: Clear mobile liquid
Stability: Several months at ambient temperature in the dark
Solubility: Soluble in acetone or ethanol, insoluble in water
Purity > 98%

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Three young adult female rabbits of the New Zealand White strain were obtained from Van Zutphen Breeding Centre, Keldonk, The Netherlands.
Date of arrival at the animal house: 27-9-'84.
From that date on, the animals, designated A1, A3 and A5, have been individually housed in metal cages with perforated floors (RUCO, Valkenswaard). Their body weights were measured 5 days before dose administration.
They were fed standard laboratory animal diet (120 g per day), obtained from Hope Fanns, Woerden ( LK - 01, pellet diameter 4 mm), and had free access to tap water. The animal room temperature was 17 - 20°C and the relative humidity 50 - 85 per cent. The artificial light sequence was 12 hours light, 12 hours dark. One day before dose administration, the fur was removed from the central back of the animals by clipping, exposing an area of the skin of approximately 15 cm x 15 cm.

Test system

Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 ml of the liquified test substance (10 min. at 40ºC)
Duration of treatment / exposure:
4 hrs
Observation period:
The animals were examined for signs of erythema and oedema and the responses were scored at 60 minutes, and approximately 24, 48 and 72 hours after removal of the dressing. The animals were al so observed 7 and 14 days after treatment.
Number of animals:
three females
Details on study design:
The test substance is applied in a single dose to the skin of the experimental animals, each animal serving as its own control. The degree of irritation is scored at specific intervals.

Administration of the test substance
0.5 ml of the liquified test substance (10 min. at 40ºC) was evenly spread on a 6 cm2 patch of surgical gauze, which was attached with a bit of petrolatum to aluminium foil and mounted on tape (Micropore®, 3M, St. Paul, USA). This was applied to the left flank of each animal, the right flank being covered with the same dressing without test substance.
Finally, the animals were wrapped in flexible bandage (Coban®, 3M, St. Paul, USA). Exposure duration was 4 hours, after which period the remaining test substance was removed, using a tissue and tap water.


Grading of the skin irritation
The following scoring system was used for grading the skin irritation:
Erythema and eschar formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to eschar
formation (injuries in depth) 4
Oedema formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well defined by
definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and
extending beyond area of exposure) 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24/72 hr
Score:
3.17
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible
Irritant / corrosive response data:
The test substance produced an inflamation to the treated skin of each animal that generally increased to well defined erythema and slight oedema during the first days after treatment and had subsided by day 7. On day 14, no significant abnormalities of the skin had remained. In no more than one animal (exp. no. A5) a mean value for skin irritation of two was observed. Concluding from these experimental results and applying the EEC criteria for classification and labelling of dangerous substances (Annex VI of Directive 67/548/EEC), the test substance can be classified as a non irritant to the skin.

Any other information on results incl. tables

Primary irritation scores for Nourycryl MC 110 in the rabbit

Rabbit No. and sex

Body weight (grams)

Observation time after exposure period (hours)

Erythema

Oedema

A1 Female

2649

1

1

2

 

 

24

1

1

 

 

48

2

2

 

 

72

2

2

 

 

Day 7

1

0

 

 

Day 14

0

0

Subtotal (a) / Mean value (c)

5/1.7

5/1.7

 

A3 Female

2426

1

1

2

 

 

24

1

1

 

 

48

2

1

 

 

72

2

2

 

 

Day 7

0

0

 

 

Day 14

0

0

Subtotal (a) / Mean value (c)

5/1.7

4/1.3

 

A5 Female

2454

1

1

2

 

 

24

1

2

 

 

48

2

2

 

 

72

2

2

 

 

Day 7

0

1

 

 

Day 14

0

0

Subtotal (a) / Mean value (c)

5/1.7

6/2

Total (b) / Mean value

15/1.7

15/1.7

a) Subtotal = sum of 24-, 48- and 72-hour score for each animal individually.

b) Total = sum of 24-, 48- and 72-hour score calculated over all animals.

c) Mean value = mean score of 24-, 48- and 72-hour reading time.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance can be classified as a non irritant to the skin.
Executive summary:

A sample of Nourycryl MC 110 was tested in the rabbit primary skin irritation test to determine its possible irritating effects. The flank skin of 3 female rabbits was exposed to the test substance for 4 hours using semi-occlusive dressing. The test substance produced an inflammation to the treated skin of each animal that increased during the first days after treatment and had subsided by day 7. The primary irritation index equals 3.17.

 

The mean values for erythema/eschar or for oedema from gradings at 24, 48 and 72 hours after patch removal were < 2.3, therefore the substance is not classified as a skin irritant according to CLP.