2-tert-butylaminoethyl methacrylate

Endpoint summary

Description of key information

2-tert-butylaminoethyl methacrylate was tested for skin irritation in rabbits; 4 hour exposure resulted in necrosis in two of the three rabbits exposed.  There is no eye irritation test available but  due to the skin corrosion it is not considered scientifically justified to test, 2-tert-butylaminoethyl methacrylate will be considered to also be corrosive to eye. 2-tert-butylaminoethyl methacrylate has not been tested for respiratory irritation, its effects on the skin would suggest that it is likely to be irritant to the respiratory tract if inhaled, but we have no specific information to confirm this

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02.01.90 - 16.05.90

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:

The test substance is a colourless to light yellow liquid at 20 °C and atmospheric pressure.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animals

The animals used in this study are male New Zealand White rabbits (6 animals), provided by the Abbey of Bellefontaine (49122 Begrolles in Mauges, France).

Upon arrival at C.I.T., the animals were acclimated to local conditions for a minimum period of 5 days, during which they are observed daily. A systematic prophylactic treatment is undertaken in order to avoid any risk of coccidial infection The treatment was administered in the drinking water as a solution of Mucoxid (R) at a dose of 137.5 mg / kg / day in a volume of 10 ml / kg (Veda-Cogla, 45140 Saint Jean de la Ruelle, France) for 5 days of the acclimatization period.

On the day of treatment, the animals had an average weight of 2.5 ± 0.1 kg. They
are individually identified by a metal ear tag.

Environment

The study was carried out in a conventional animal area. The Environment was maintained during the acclimatization period and for the study as follows:

Temperature : 20+/- 3°C
Humidity : 50 +/- 20% relative humidity
Light cycle : 12 hours light and 12 hours dark

The temperature and humidity are recorded for each animal room. The air is not recycled it is filtered through an absolute filter.

The rabbits were housed individually in polystyrene cages equipped with a fodd contained and a water bottle.

The rabbits were fed a granular rabbit diet (No 112 C UAR 91360 Villemoisson-sur-Orge, France), ad libitum for the duration of the study. A certificate of analysis was included in the report. The drinking water was filtered through a 0.22 micron membrane. The water was regularly checked for bacteriological and chemical contamination
Animals

The animals used in this study are male New Zealand White rabbits (6 animals), provided by the Abbey of Bellefontaine (49122 Begrolles in Mauges, France).

Upon arrival at C.I.T., the animals were acclimated to local conditions for a minimum period of 5 days, during which they are observed daily. A systematic prophylactic treatment is undertaken in order to avoid any risk of coccidial infection The treatment was administered in the drinking water as a solution of Mucoxid (R) at a dose of 137.5 mg / kg / day in a volume of 10 ml / kg (Veda-Cogla, 45140 Saint Jean de la Ruelle, France) for 5 days of the acclimatization period.

On the day of treatment, the animals had an average weight of 2.5 ± 0.1 kg. They
are individually identified by a metal ear tag.

Environment

The study was carried out in a conventional animal area. The Environment was maintained during the acclimatization period and for the study as follows:

Temperature : 20+/- 3°C
Humidity : 50 +/- 20% relative humidity
Light cycle : 12 hours light and 12 hours dark

The temperature and humidity are recorded for each animal room. The air is not recycled it is filtered through an absolute filter.

The rabbits were housed individually in polystyrene cages equipped with a fodd contained and a water bottle.

The rabbits were fed a granular rabbit diet (No 112 C UAR 91360 Villemoisson-sur-Orge, France), ad libitum for the duration of the study. A certificate of analysis was included in the report. The drinking water was filtered through a 0.22 micron membrane. The water was regularly checked for bacteriological and chemical contamination

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Preparation of the Animals

Before treatment the flanks of the animals were clipped using electric clippers. The rabbits were then checked to ensure there were no signs of skin irritation prior to treatment.

Treatment

0.5ml of the test substance was placed on hydrophilic gauze of 6cm2, which was then applied to the right side of each animal. The left flank where no test substance was applied served as the control. The gauze was secured on the skin by menas of a semi-ventilated hypoallergenic adhesive dressing.

Duration of treatment / exposure:

The test substance was applied to the skin for three minutes for rabbits No 4-6 and 4 hours for rabbits No 1-3. The skin was not washed when the gauze was removed

Observation period:

The skin reactions were evaluated 1 hour and then 24, 48 and 72 hours after removal of the gauze to assess the reversibility of the reactions, following the scoring system found in guideline OECD 404. Obervations were continued until day 9.

Number of animals:

Male New Zealand white rabbits, 3 exposed for 3 minutes and 3 exposed for 4 hours.

Details on study design:

The test substance was applied to the skin for three minutes for rabbits No 4-6 and 4 hours for rabbits No 1-3. The skin reactions were evaluated 1 hour and then 24, 48 and 72 hours after removal of the gauze to assess the reversibility of the reactions, following the scoring system found in guideline OECD 404. Obervations were continued until day 9.

Irritation parameter:

erythema score

Remarks:

3 min exposure

Basis:

mean

Time point:

24/48/72 h

Score:

2.7

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

edema score

Remarks:

3 min exposure

Basis:

mean

Time point:

24/48/72 h

Score:

1.8

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

erythema score

Remarks:

4 h exposure

Basis:

mean

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 9 days

Remarks:

Two animals sacrificed at day 2

Irritation parameter:

edema score

Remarks:

4 h exposure

Basis:

mean

Time point:

24/48/72 h

Score:

3.4

Max. score:

4

Reversibility:

fully reversible within: 9 days

Remarks:

Two animals sacrificed at day 2

Irritant / corrosive response data:

RESULTS

Application for 3 minutes:

After one hour, a visible erythema was observed in 3 animals. After 24 hours the erythema remains clearly visible and a slight edema was apparent. After 48 hours, the erythema became moderate to severe, the oedema remained slight. After 72 hours the oedema disappeared in one animal but the other lesions persisted.

At day 5, no oedema was observed, the oedema regressed in one animal. During days 6 to 8 erythema regressed and disappeared with dryness of the skinj noted on three animals. By day 9 no skin lesion were recorded.

Application for 4 hours:

After one hour, a severe erythema or signs of necrosis associate has a slight edema was seen in one animal and severe oedema in 2 animals was seen. After 24 hours, signs of necrosis were seen in two animals which were terminated at that time. The skin reactions in the third animal were significant up to day 5 but then regressed and disappeared by day 9.

As necrosis was seen which resulted in the termination of 3 of the four rabbits, the classification was for R34, this is Category 1C against the EU CLP(GHS) criteria.

Table 1

 

Application for 3 minutes

 

Average scores calculated for each site

 

	Observation	Time			Maximum
	1 hour	24 hours	48 hours	72 hours	Possible score
Erythema	2.0	2.0	3.0	3.0	4
Oedema	0.0	2.0	2.0	1.3	4

 

Average scores calculated from the scores at 24.48 and 72 hours four each animal

	Animal No			Maximum score
	04	05	06	Per site
Erythema	2.7	2.7	2.7	3 for 3 days
Oedema	2.0	1.3	2.0	2 for 3 days

 

Tables 2/3

 

Application for 3 minutes

 

No of Rabbits	Day 1	Day 2	Day 3	Day4	Day5	Day6	Day7	Day8	Day9
	1hour	24hour	48hour	72hour
Erythema
04	2	2	3	3	3	2/S	1/S	0/S	0
05	2	2	3	3	3	2/S	1/S	0/S	0
06	2	2	3	3	2/S	2/S	1/S	0/S	0
Oedema
04	0	2	2	2	0	0	0	0	0
05	0	2	2	0	0	0	0	0	0
06	0	2	2	2	0	0	0	0	0

S= Dryness of the skin

 

Table 4

 

Application for 4 hours

 

Average scores calculated for each site

 

	Observation	Time			Maximum
	1 hour	24 hours	48 hours	72 hours	Possible score
Erythema	3.3(1)	3.7(1)	3.0	3.0	4
Oedema	3.3	4.0	3.0	2.0	4

(1) Calculated on the basis N = 4

 

Average scores calculated from the scores at 24.48 and 72 hours four each animal

	Animal No			Maximum score
	04	05	06	Per site
Erythema	(2)	3.0	(2)	Necrosis
Oedema	(2)	3.0	(2)	4 after 24 hours

(2) = Animal sacrificed on day 3

 

Tables 5/6

 

Application for 4 hours

No of Rabbits	Day 1	Day 2	Day 3	Day4	Day5	Day6	Day7	Day8	Day 9
	1hour	24hour	48hour	72hour
Erythema
01	N	N	(1)	(1)	(1)	(1)	(1)	(1)	(1)
02	2	3	3	3	2	1/S	0/S	0/S	0
03	4	N	(1)	(1)	(1)	(1)	(1)	(1)	(1)
Oedema
01	4	4	(1)	(1)	(1)	(1)	(1)	(1)	(1)
02	2	4	3	2	0	0	0	0	0
03	4	4	(1)	(1)	(1)	(1)	(1)	(1)	(1)

(1) Animal sacrificed N=Necrosis S= Dryness of skin

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this experiment , taking into account the classification criteria at the time of the experiment 83/467/EEC, MATBAE is considered to be irrigating after 3 minute exposure but was corrosive to the skin of rabbits after 4 hour exposure. This would result in a classification under the EU CLP (GHS) classification criteria of category 1C.

Executive summary:

SUMMARY

The study investigated if skin irritation can be induced by MATBAE (t-butylaminoethyl methacrylate) when evaluated in rabbits in accordance with the guideline No. 404 (OECD 1981) the study was carried out under the requirements for Good Laboratory Practice (OECD 1981). The interpretation of the results was performed according to the criteria of classification described in the Directive 83/467/EEC of 29 July 1983 on the fifth adaptation to technical progress
of Directive 67/548/EEC.

Materials and Methods

A single dose of 0.5 ml of the product has been prepared on a dry gauze then applied to a skin surface mowed 6 cm2 in 6 males New Zealand White rabbits. The product was kept in contact with skin for 3 minutes in 3 animals and 4 hours in 3 other animals
using a semi-dressing occlusive application. The skin reactions were observed at
1 hour, 24, 48 and 72 hours after the removal of the dressings and then daily to monitor reversibility or irreversibility. No rinsing of the product from the skin was made after the removal of the dressing

 

Results

Application of the product for 3 minutes:

The reactions that were consistently observed were of marked skin erythema and oedema (individual scores of 2 or 3) for at least 72 hours in three animals. Dryness of skin was also observed at the site of application of the product between day 5 and day 8. By day 9, all lesions skin effects are reversible.

Application of the product for 4 hours:

The observed skin reactions were severe (necrosis in one animated after
1 hour, and in 2 animals after 24 hours, with severe oedema in 3 animals). The skin lesions on the rabbit which showed no evidence of necrosis, were reversible by day 9. The other two animals were sacrificed after 24 hours due to the serious nature of the corrosive effects on the skin.

 

Conclusion

Under the conditions of this experiment , taking into account the classification criteria at the time of the experiment 83/467/EEC, MATBAE is considered to be irrigating after 3 minute exposure but was corrosive to the skin of rabbits after 4 hour exposure. This would result in a classification under the EU CLP (GHS) classification criteria of category 1C.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

2-tert-butylaminoethyl methacrylate showed clear corrosive effects on the skin in rabbits after exposures for 4 hours. There is no test data for eye irritation but the effects seen in the skin indicate that 2-tert-butylaminoethyl methacrylate would be corrosive also to eyes.  The hazard phrase H314 that is required for Category 1C skin corrosion is Causes severe skin burns an eye damage, so this expected hazard will be adequately warned against without the need for an animal study. Such a study would be scientifically unjustified for a corrosive substance due to animal welfare considerations. We have no test data for respiratory irritation. Inhalation is not an expected route of exposure as this substance is manufactured and used under but based on its skin corrosion 2-tert-butylaminoethyl methacrylate would be expected to cause irritation to the respiratory tract if inhaled. However in the absence of any specific information it is not considered that a classification is required under EU CLP (GHS) for respiratory irritation.

Justification for selection of skin irritation / corrosion endpoint:

There is a skin irritation study in rabbits, which is Klimisch 1 as it is GLP compliant and to the OECD guideline 404.  The test substance identified as MATBAE a French abbreviation of t-butylamino ethyl methacrylate.  Exposure was for either 3 minutes or 4 hours. 2-tert-butylaminoethyl methacrylate was a marked skin irritant after the 3 minute exposure but it was corrosive with necrosis of the skin seen in two of the three rabbits tested.

Justification for selection of eye irritation endpoint:

There is no study available for eye irritation in rabbits for 2-tert-butylaminoethyl methacrylate.   However as 2-tert-butylaminoethyl methacrylate is corrosive to skin it can be assumed that it would also be corrosive to eyes.  The Hazard phrase that is applied with the category 1C for skin corrosion is Causes severe skin burn and eye damage, so this hazard will be suitable warned against.  Due to the corrosive properties it would not be ethically acceptable to perform an eye irritation study in animals.

Effects on skin irritation/corrosion: corrosive

Justification for classification or non-classification

2-tert-butylaminoethyl methacrylate showed clear corrosive effects to the skin in rabbits after exposures for 4 hours. Therefore 2-tert-butylaminoethyl methacrylate is classified as Category 1C for skin corrosion by the EU CLP (GHS) criteria.

2-tert-butylaminoethyl methacrylate has not been tested in rabbits but serious damage to eyes can be expected due to the corrosive properties seen in the skin therefore it is classified as Category 1 for eye damage/irritation by the EU CLP (GHS) criteria.

In the absence of any specific data on irritation to the respiratory tract from inhalation of 2-tert-butylaminoethyl methacrylate it is not proposed to classify for respiratory irritation.