2-(1-oxa-4-azaspiro[4.5]dec-4-yl)ethyl methacrylate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Initiation date: 04-11-1986, Completion date: 25-11-1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-(1-oxa-4-azaspiro[4.5]dec-4-yl)ethyl methacrylate

EC Number:

224-116-8

EC Name:

2-(1-oxa-4-azaspiro[4.5]dec-4-yl)ethyl methacrylate

Cas Number:

4203-89-8

Molecular formula:

C14H23NO3

IUPAC Name:

2-{1-oxa-4-azaspiro[4.5]decan-4-yl}ethyl 2-methylprop-2-enoate

Test material form:

liquid

Specific details on test material used for the study:

Chemical name (IUPAC): Methacrylic acid, 2-(1 oxa-4-aza spiro [4,5] dec-4-yl ethyl ester)
Commercial name: Nourycryl MA 128
Batch no.: 860930 - DT4
Purity: >99%; major impurity p -methoxyphenol (100 ppm)
Solubility: Soluble in ethanol and toluene, decomposes in water
Appearance: Clear slightly yellow liquid
Storage: At ambient temperature in the dark in the presence of silica gel

Test animals

Species:

rabbit

Strain:

not specified

Test system

Type of coverage:

not specified

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

yes, concurrent negative control

Amount / concentration applied:

not specified

Duration of treatment / exposure:

single application

Observation period:

The exposed skin areas were examined for signs of erythema and oedema and the responses were scored at 60 minutes, and approximately 24, 48 and 72 hours, and 7, 14 and 21 days after removal of the patches. For reference the control site on the contralateral flank was used. In order to facilitate the scoring, the skin area concerned of all animals was shaved again at least 5.5 hours before the observations on day 1, 3, 7, 14 and 21.

Number of animals:

three

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 1-3

Time point:

24/48/72 h

Score:

>= 2 - <= 4

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

animal: 1-3

Time point:

24/48/72 h

Score:

>= 2 - <= 3

Max. score:

3

Reversibility:

other: reversibility not clear due to eschar formation

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

One hour after removal the test substance the skin of all three rabbits showed well-defined erythema and obvious to moderate oedema. The erythema increased to severe followed by eschar formation, in animal 3095 already after 24 hours, while animals 3097 and 3099 showed eschar formation on day 7. During the following weeks the treated skin did not heal, all three rabbits revealed eschar formation and a slightly thicker and less flexible skin. When the study was terminated on day 21, the exposed skin of animals 3097 and 3099 showed no or very little hair growth, less flexibility and clear reddening indicating chronic dermal inflammation. In animal 3095, the skin revealed the same symptoms and also scar tissue. Signs of systemic intoxication were not observed in any of the rabbits. The calculated primary irritation index (modified) is 5.0.

Any other information on results incl. tables

Primary Skin Irritation Scores For Nourycryl MA 128 in the Rabbit

Rabbit no. and sex	Body weight (grams)	Observation time after exposure period (hours)	Erythema	Oedema
3095, female	2744	1	2	3
		24	4h)	3
		48	4h)	2
		72	4h)	3
		Day 7	4	_d)
		Day 14	4	_d)
		Day 21	_g)	_e)
Subtotal a)/Mean value c)			12/4.0	8/2.7
3097, female	2457	1	2	2
		24	2	2
		48	2	2
		72	2	2
		Day 7	4	_d)
		Day 14	_f)	0
		Day 21	_f)	_e)
Subtotal a)/Mean value c)			6/2.0	6/2.0
3099, female	2697	1	2	2
		24	2	2
		48	2	2
		72	2	2
		Day 7	4	_d)
		Day 14	_f)	0
		Day 21	_f)	_e)
Subtotal a)/Mean value c)			6/2.0	6/2.0
Total a)/Mean value c)			24/2.7	20/2.2

 

Notes

a) Subtotal = sum of 24-, 48 - and 7 2 -hour scores for each animal individually

b) Total = sum of 24-, 48- and 7 2 -hour scores calculated over all animals.

c) Mean value = mean score of 24-, 48 - and 7 2 -hour reading times.

d) Difficult to score due to eschar formation.

e) Treated skin slightly thicker and less flexible than normal.

f) No or very little hair growth, exposed skin clearly red.

g) No hair growth, exposed skin clearly red with white areas of scar tissue.

h) The exposed skin revealed partial necrosis.

 

Primary irritation index (modified)*= 5.0

* Total of 24- and 7 2-hour scores for erythema and oedema, divided by 6.

It should be noted that the original Draize primary skin irritation index applies to the combined average of the scores for intact and abraded skin. In this study the test substance was applied to intact skin.

Applicant's summary and conclusion

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Remarks:

After 4 hr exposure; 1/3 animals showed necrosis after 24 hr and scar tissue visible after 21 days.

Conclusions:

The calculated primary irritation index (modified) is 5.0. One animal showed visible necrosis and effects were not fully reverisble within 21 days. The substance was found to be corrosive to skin.

Executive summary:

The purpose of the study was to evaluate local irritating or corrosive effects on the rabbit skin following a single application of the test substance. The study was performed according to OECD TG 404.

One hour after removal the test substance the skin of all three rabbits showed well-defined erythema and obvious to moderate oedema. The erythema increased to severe followed by eschar formation, in animal 3095 already after 24 hours, while animals 3097 and 3099 showed eschar formation on day 7; During the following weeks the treated skin did not heal, all three rabbits revealed eschar formation and a sslightly thicker and less flexible skin. When the study was terminated on day 21, the exposed skin o f animals 3097 and 3099 showed no or very little hair growth, less flexibility and clear reddening indicating chronic dermal inflammation. In animal 3095, the skin revealed the same symptoms and also scar tissue. Signs o f systemic intoxication were not observed in any of the rabbits.

The substance was found to be corrosive to skin and classified as Category 1C (corrosive) based on GHS criteria.