4-(1,1-dimethylethyl)cyclohexyl methacrylate

Endpoint summary

Description of key information

The mean skin irritation scores in a GLP in vivo study were < 2.3 and the test substance is not irritating to the skin. It was concluded that the test substance is a non-irritant to the eye based on an in vivo GLP study.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

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%

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.

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

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.

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.

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.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Initiation date: 27-11-'84 Completion date: 30-11-'84

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

Specific details on test material used for the study:

Chemical name (IUPAC): t-Butyl cyclohexyl methacrylate
Trade name/code: Nourycryl MC 110
Appearance: Clear mobile liquid
Storage: At ambient temperature in the dark
Purity > 98%

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Three 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: 27-09-'84. From that date on, the animals, designated A1, A2 and A3, have been individually housed in metal cages with perforated floors (RUCO, Val kenswaard). Their body weights were measured 5 days before dose administration. They were fed standard laboratory animal diet (120 g per day), obtained from Hope Farms, Woerden (LK-01, pellet diameter 4 mm), and had free access to tap water,. The animal room temperature was 20 ± 1 ºC and the relative humidity 50-70 percent. The artificial light sequence was 12 hours light, 12 hours dark.

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.1ml undiluted test item

Duration of treatment / exposure:

single treatment

Observation period (in vivo):

The eyes were examined 1 hour and approximately 24, 48 and 72 hours after instillation of the test substance.

Number of animals or in vitro replicates:

three females

Details on study design:

Administration of the test substance
The animals were held in a physical restrainer (Tecniplast, Italy) during dose administration. 0.1 ML of the test substance was instilled in the conjunctival sac of the right eye of each animal using a syringe. The lids were then held gently together for two seconds-and released. Immediately after treatment, the animals were transferred to their cages. The left eye, remaining untreated, served as a control.

Observations
Prior to dose administration, both eyes of the animals were inspected in order to detect any eye defect. Immediately after instillation of the test substance, the animals were observed and abnormalities were recorded. In addition, the eyes were examined 1 hour and approximately 24, 48 and 72 hours after instillation of the test substance.

Fluorescein treatment
Approximately twenty-four hours after instillation of the test substance (immediately after scoring the corneal opacity and alterations of iris and conjunctivae), a solution of 2% fluorescein in water (pH adjusted to 7 .0) was applied to both eyes of each animal to quantitatively examine the potential for corneal injury. The brightly green staining area indicating epithelial damage was estimated as a percentage of the total corneal area.
Any observed local effects other than those indicated above were recorded.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

One hour after test substance instillation slight reddening of the conjunctivae was observed in all animals and swelling of the eye lids in two animals. However, 24 hours after treatment no effects on the cornea, the iris and the conjunctivae had remained in any of the rabbits. Treatment of
the eyes with fluorescein 24 hours after instillation of the test substance did not reveal any epithelial damage.
According to the criteria laid down in Annex VI of the EEC Council Directive 67/548/EEC, the test substance can be classified as a non-irritant to the eye.

 Eye irritation scores for Nourycryl MC110 in the rabbit

Rabbit No. and sex	Body weight (grams)	Observation time after exposure period (hours)	Cornea opacity	Iris lesion	Conjunctival redness	Conjunctival Swelling (chemosis)
A1 Female		1	0	0	1	2
		24	0	0	0	0
		48	0	0	0	0
		72	0	0	0	0
Subtotal (a) / Mean value (c)			0/0	0/0	0/0	0/0
A3 Female	2426	1	0	0	1	0
		24	0	0	0	0
		48	0	0	0	0
		72	0	0	0	0
Subtotal (a) / Mean value (c)			0/0	0/0	0/0	0/0
A5 Female	2454	1	0	0	1	1
		24	0	0	0	0
		48	0	0	0	0
		72	0	0	0	0
Subtotal (a) / Mean value (c)			0/0	0/0	0/0	0/0
Total (b) / Mean value			0/0	0/0	0/0	0/0

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

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

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

Interpretation of results:

GHS criteria not met

Conclusions:

24 hours after treatment no effects on the cornea, the iris and the conjunctivae had remained in any of the rabbits. Treatment of the eyes with fluorescein 24 hours after instillation of the test substance did not reveal any epithelial damage.
Therefore the substance is not classified for eye irritation according to CLP.

Executive summary:

A sample of Nourycryl MC 110 was tested in the rabbit acute eye irritation test to determine its possible irritating effects. No persistent effects were observed during the 72-hour observation period following instillation of 0.1 ml of the test substance into the left eye of 3 adult female rabbits. Therefore it is concluded that the test substance is a non-irritant to the eye.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The substance is not irritating to the skin and is a non-irritant to the eye. Data are conclusive and not suffficient for classification.