2-tert-butylaminoethyl methacrylate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation, other

Remarks:

in vivo none LLNA

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented GLP study to OECD guidelines study includes certificate of analysis for the testsubstance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

t-butylaminoethyl methacrylate (MATBAE)

IUPAC Name:

t-butylaminoethyl methacrylate (MATBAE)

Constituent 2

Reference substance name:

2-tert-butylaminoethyl methacrylate

EC Number:

223-228-4

EC Name:

2-tert-butylaminoethyl methacrylate

Cas Number:

3775-90-4

Molecular formula:

C10H19NO2

IUPAC Name:

2-(tert-butylamino)ethyl 2-methylprop-2-enoate

Test material form:

other: liquid

Details on test material:

- protocol: t-BUTYLAMINOETHYL METHACRYLATE (MATBAE)
- labelling: t-BUTYLAMINOETHYL METHACRYLATE
batch number:
- protocol and labelling: 1/96
Elf Atochem filing number: CAL 4357/96
• description: colourless liquid
container: one aluminium flask
• date of receipt: 8 August 1996
• storage conditions: at room temperature and protected from light
• purity: 99.66%.

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

Animals
Species and strain: Dunkin-Hartley guinea-pigs.
Reason for this choice: species recommended by the international regulations for sensitization studies. The strain used has been shown to produce a satisfactory sensitization response using known positive sensitizers.
Breeder: Centre d'Elevage Lebeau, 78950 Gambais, France.
Number: 30 animals (15 males and 15 nulliparous and non-pregnant females).
Allocation of the animals to the groups: on day -1, the animals were weighed and randomly allocated to two groups: a control group 1 consisting of ten animals (five males and five females) and a treated group 2 consisting of 20 animals (ten males and ten females). Weight: on day 1, the animals were approximately three months old and had a mean bodyweight ± standard deviation of 374 ± 29 g for the males and 338 ± 18 g for the females.
Acclimatization: at least five days before the beginning of the study.
Identification of the animals: ear-tattoo.

Environmental conditions
During the acclimatization period and throughout the study, the conditions in the animal room were set as folIows:
temperature: 21 ± 2°C
relative hurnidity: 30 to 70%
light/dark cycle: 12 h/12 h
ventilation: about 12 cycles/hour of filtered, non-recycled air.
The temperature and relative humidity were recorded continuously and records retained.
The housing conditions (temperature, relative humidity and ventilation) were checked monthly.
During the acclimatization period and throughout the study, the animals were housed individually in polycarbonate cages (48 cm x 27 cm x 20 cm) equipped with a polypropylene bottle.
Dust-free sawdust was provided as litter (SICSA, 92142 Alfortville, France).
Bacteriological analysis of the sawdust and detection of possible contaminants (pesticides, heavy metals) are performed periodically.

Results and discussion

Positive control results:

See attached Appenix 4. at 0.1% intradermal induction and 1% cutaneous induction fowwoed by 0.5% challenge, vehicle was paraffin oil. 50% of the guinea pigs reacted.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 3

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

Challenge dose 50%

No. with + reactions:

4

Total no. in group:

20

Clinical observations:

well defined erythema

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Challenge dose 50%. No with. + reactions: 4.0. Total no. in groups: 20.0. Clinical observations: well defined erythema.

Results 4

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

Challenge dose 50%

No. with + reactions:

6

Total no. in group:

20

Clinical observations:

well defined erythema

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Challenge dose 50%. No with. + reactions: 6.0. Total no. in groups: 20.0. Clinical observations: well defined erythema.

Any other information on results incl. tables

Challenge application

No residual test substance was observed after removal of the dressing.

 

Skin reactions were as follows:

Sex	Animal number	Control Group
		24 hours					48 hours
		Erythema			Oedema		Erythema			Oedema
		LF	RF	LF		FR	LF	RF	LF		RF
Male	26	0	0	0		0	0	0	0		0
	27	0	0	0		0	0	0	0		0
	28	0	0	0		0	0	0	0		0
	29	0	0	0		0	0	0	0		0
	30	0	0	0		0	0	0	0		0
Female	41	0	0	0		0	0	0	0		0
	42	0	0	0		0	0	0	0		0
	43	0	0	0		0	0	0	0		0
	44	0	0	0		0	0	0	0		0
	45	0	0	0		0	0	0	0		0

 

Sex	Animal number	Treated Group
		24 hours					48 hours
		Erythema			Oedema		Erythema			Oedema
		LF	RF	LF		FR	LF	RF	LF		RF
Male	31	0	0	0		0	0	0	0		0
	32	0	1	0		0	0	2	0		0
	33	0	1	0		0	0	2/A	0		0
	34	0	1	0		0	0	0	0		0
	35	0	0	0		0	0	1	0		0
	36	0	1	0		0	0	0	0		0
	37	0	1	0		0	0	1/S	0		0
	38	0	1	0		0	0	1/S	0		0
	39	0	1	0		0	0	1/S/A	0		0
	40	0	1	0		0	0	1/S	0		0
Female	46	0	0	0		0	0	2	0		0
	47	0	2	0		0	0	2	0		0
	48	0	0	0		0	0	0	0		0
	49	0	1	0		0	0	0	0		0
	50	0	2	0		0	0	2	0		0
	51	0	1	0		0	0	0	0		0
	52	0	0	0		0	0	0	0		0
	53	0	0	0		0	0	0	0		0
	54	0	2	0		0	0	2/S	0		0
	55	0	0	0		0	0	0	0		0

LF: left flank (control)

RF: right flank (treated)

S : dryness of the skin

A : crusts

 

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions and according to the maximization method of Magnusson and Kligman, cutaneous reactions attributable to the sensitization potential of the test substance t-BUTYLAMINOETHYL METHACRYLATE (MATBAE) (batch No. 1/96) were observed in 6/20 (30%) guinea-pigs. This results in a classification of Category 1B for skin sensitization by the EU CLP(GHS) criteria.

Executive summary:

At the request of Elf Atochem S.A., Paris-Ia-Defense, France, the potential of the test substance

t-BUTYLAMINOETHYL METHACRYLATE (MATBAE) (batch No. 1/96) to induce delayed contact hypersensitivity was evaluated in guinea-pigs according to the maximization method of Magnusson and Kligman and to O.E.C.D. (No. 406, 17th July 1992) and E.C. (92/69/E.E.C)., B6, 31 st July 1992) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

 

Methods

Thirty guinea-pigs were allocated to two groups: a control group 1 (five males and five females) and a treated group 2 (ten males and ten females). On day I, intradermal injections of Freund's complete adjuvant mixed with the test substance (treated group) or the vehicle (control group) were performed in the dorsal region between the shoulders. On day 7, the same region received a topical application of sodium lauryl sulfate in Vaseline (10% w/w) in order to induce local irritation.

 

On day 8, this same test site was treated by topical application of the test substance (treated group) or the vehicle (control group) and was covered by an occlusive dressing for 48 hours. On day 22, after a rest period of 12 days, all animals of the treated and control groups were challenged by a topical application of the test substance to the right flank. The left flank served as control and received the vehicle only. Test substance and vehicle were maintained under an occlusive dressing for 24 hours. Skin reactions were evaluated approximately 24 and 48 hours later.

 

Test substance concentrations were as follows:

 

Induction (treated group)

 

intradermal injections: t-BUTYLAMINOETHYL METHACRYLATE (MATBAE) at 1% (w /w) in paraffin oil

topical application: t-BUTYLAMINOETHYL METHACRYLATE (MATBAE) at 50% (w/w) in paraffin oil.

 

Challenge (all groups)

 

topical application: t-BUTYLAMINOETHYL METHACRYLATE (MATBAE) at 50% (w/w) in paraffin oil.

 

At the end of the study, animals were killed and cutaneous sampIes were taken from the challenge application sites from all the animals. No histological examinations were performed.

 

The sensitivity of the guinea-pigs in C.I.T. experimental conditions was checked with a positive sensitizer: 2,4-DINITRO CHLOROBENZENE. During induction period, the positive substance was applied at 0.1% (w/w) (day 1) and 1% (w/w) (day 8) concentrations. At cutaneous challenge application, a 0.5% (w/w) concentration was tested on the right flank.

 

Results

No clinical signs and no deaths were noted during the study. After the cutaneous challenge application, no cutaneous reactions were noted in the control group. In the treated group, at the 24-hour reading, a very slight or well-defined erythema was noted in 11120 and4/20animals, respectively. At the 48-hour reading, a very slight or well-defined erythema was still observed in5120and6/20animals, respectively. Dryness of the skin was also observed in5/20animals, and crusts in2120animals.

 

The guinea-pigs showed a satisfactory sensitization response in 50% animals using a positive

Sensitizer (Appendix 4).

 

Conclusion

Under our experimental conditions and according to the maximization method of Magnusson

and Kligman, cutaneous reactions attributable to the sensitization potential of the test substance

t-BUTYLAMINOETHYL METHACRYLATE (MATBAE) (batch No. 1196) were observed in

6/20(30%) guinea-pigs. This results in a classification of Category 1B for skin sensitization by the EU CLP(GHS) criteria.