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

Endpoint summary

Description of key information

The substance was found to be corrosive to skin and non-irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

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

Reference 2

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

not specified

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

Species:

rabbit

Strain:

not specified

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

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

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Reference 1

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

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Initiation date: 25-11-1986, Completion date: 28-11-1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

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): Methacrylic acid, 2-(1 oxa-4- aza spiro [4, 5] dec-4-yl ethyl ester
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

Species:

rabbit

Strain:

not specified

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

not specified

Duration of treatment / exposure:

single treatment

Observation period (in vivo):

43 minutes, 24 hr, 48 hr and 72 hr

Number of animals or in vitro replicates:

three female rabbits

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

Basis:

mean

Time point:

24/48/72 h

Score:

0.2

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

positive 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:

Instillation of the test substance into one of the eyes of three female rabbits slightly affected the conjunctivae. Approximately 43 minutes after exposure all three animals showed slight conjunctival redness only. In animals 3077 and 3083 the reddening had disappeared the next day and in animal 3081, 72 hours after instillation of the test substance.
Adverse effects on the cornea and the iris were not observed in any of the rabbits during the entire observation period. Treatment of the eyes with fluorescein 24 hours after instillation of the test substance did not reveal any epithelial damage. During the first few hours after exposure lacrimation was observed in all rabbits and in animal 3083 discharge was slightly higher.
Signs of systemic intoxication were not observed. Based on the calculated Oraize score of 2 (1 hour) the test substance should be classified as minimally irritating according to the scheme of Kay and C alandra (1962). According to the EEC criteria for classification and labelling of dangerous substances, the test substance need not be labelled as an eye-irritant.

Interpretation of results:

GHS criteria not met

Conclusions:

According to the EEC criteria for classification and labelling of dangerous substances, the test substance need not be labelled as an eye-irritant.

Executive summary:

The purpose of the study was to evaluate the ability of the test substance to produce ocular irritation or corrosion in the rabbit following a single. application to the eye. The substance was found to be a non-irritant. According to the EEC criteria for classification and labelling of dangerous substances, the test substance need not be labelled as an eye-irritant.

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 was found to be corrosive to skin (Cat. 1C) and non-irritating to eyes.