2-amino-2-methylpropanol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not applicable

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: meets generally accepted scientific standards, well-documented, and acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The test guideline followed:
An intradermal sensitization test was conducted by intradermally injecting AMP (P-1826 ) into male guinea pigs according to Landsteiner and Jacobs procedure (Landsteiner, K. , and J. Jacobs. Itstudies on sensitization of Animals with Simple Chemical Compo~nds.~J . Ex.. Med. -61: 643-656, 1935).

Guinea pigs are exposed to the test substance, positive control or vehicle control via intra dermal injection. Test material and positive control solutions will be prepared fresh for each intradermal injection, A total of 1 0 injections will be made on alternate days, three times a week, over a four week period. After each injection, the site will be scored, Each injection will be made at a different location along the side. After the last injection, the animals will be allowed to rest for two weeks. A challenge injection will be made a t a virgin site. The site will be scored for erythema and edema at 24 and 48 h,
If needed, the animals will be rechallenged a t another site after the last reading of the first challenge.

GLP compliance:

no

Type of study:

intracutaneous test

Justification for non-LLNA method:

This study was already available.

Test material

Test material information

Constituent 1

Reference substance name:

2-amino-2-methylpropanol

EC Number:

204-709-8

EC Name:

2-amino-2-methylpropanol

Cas Number:

124-68-5

Molecular formula:

C4H11NO

IUPAC Name:

2-amino-2-methylpropan-1-ol

Details on test material:

- Name of test material (as cited in study report): AMP; P-1826
- Lot/batch No.: Lot #9B02-9B
- Analytical purity: 2-Amino-2-methyl-1-propanol 99.34% by w t

In vivo test system

Test animals

Species:

guinea pig

Strain:

not specified

Sex:

male

Details on test animals and environmental conditions:

Thirty male guinea pigs (250-300g each) were divided into 3 groups of 10 each. The animals' backs and flanks were shaved free of hair. The guinea pigs were intradermally-injected with the solutions.

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

water

Induction 2

Concentration / amount:

Induction- 0.05mL of 1% (one dose), 0.5% (one dose) and 0.1% (remaining 8 doses) P-1826 solution
Challenge- 0.1mL of 0.05% and 0.01% solutions of P-1826

Challenge

Challenge 1

Route:

intradermal

Vehicle:

water

Challenge 2

Concentration / amount:

Induction- 0.05mL of 1% (one dose), 0.5% (one dose) and 0.1% (remaining 8 doses) P-1826 solution
Challenge- 0.1mL of 0.05% and 0.01% solutions of P-1826

No. of animals per dose:

10

Details on study design:

One group was treated with 0.05mL of 1% P-1826 solution, a negative control group was treated with saline, and a positive control group was treated with dinitrochlorobenzene (DNCB solubilized in alcohol and made to volume with saline). After 24 hours, sites were cleaned and scored for erythema and edema according to Draize (Draize, JH, "Appraisal of the Safety of Chemicals in Foods, Drugs, and Cosmetics". Assoc. of Food and Drug Officials of the United States, p. 48, 1957). At 48 hours, the application was repeated with each group, and continued 2-3 times per week until 10 applications were made. Animals were allowed a 2 week recovery period, and then challenged at a virgin site. The test and negative control animals were challenged with 0.1mL of 0.05% and 0.01% solutions of P-1826. Positive and negative control animals were also challenged with 0.3% and 0.03% DNCB solution. After 24 hours, they were depilated, and three hours later scored for erythema and edema. Sites were scored again at 48 hours.

Test material is considered a sensitizer if the challenge elicits skin reactions in a large number of test animals when compared to the negative control.

A re challenge was necessary, thus the test material was injected again at a virgin site in both test group and the negative control.

Challenge controls:

Yes

Positive control substance(s):

yes

Remarks:

dinitrochlorobenzene (DNCB solubilized in alcohol and made to volume with saline)

Results and discussion

Positive control results:

A challenge with 0.3% DNCB in the positive control group caused inflammation in all 10 treated animals at 24 hours, and the reaction persisted in 2 animals at 24 hours. The 0.03% solution elicited an inflammation response in 7 out of the 10 treated animals at 24 hours, this inflammation did not persist until 48 hours in any of the animals. The positive control was thus considered valid.

In vivo (non-LLNA)

Results

Remarks on result:

no indication of skin sensitisation

Remarks:

detailed results are provided in below section

Any other information on results incl. tables

During the induction phase, the first injection at 1% and second injection at 0.5% P-1826 induced necrotic lesions, so the remaining 8 injections were made with 0.1% solutions.  The 0.3% DNCB sites were necrotic for the entire 10 injections.

At challenge with 0.05% and 0.01% P-1826, one animal in the test group showed mild reactions with 0.05%, and none of the negative controls challenged with P-1826 showed any reactions at 24 or 48 hours.  In the repeat challenge, none of the animals in the test group showed any reactions with P-1826, but of the negative control group, 4 animals at 0.05% and 1 animal at 0.01% showed skin reactions at 24 hours.

These results are summarised in the below table:

	Test group				Positive Control				Negative Control
Material	P-1826 (AMP)				DNCB				Saline
No. Of animals	10				10				10
Induction dose	1.0/0.5/0.1%				0.3				0.9
Challenge material	P-1826 (AMP)				DNCB				P-1826 (AMP)
Challenge conc.	0.05%		0.01%		0.3%		0.03%		0.05%		0.01%
Skin Reaction scored at (h)	24	48	24	48	24	48	24	48	24	48	24	48
No. reacted/No. Challenged	1/10	0/10	0/10	0/10	10/10	2/10	7/10	0/10	0/10	0/10	0/10	0/10
Repeat Challenge
Challenge material	P-1826 (AMP)								P-1826 (AMP)
Challenge conc.	0.05%		0.01%						0.05%		0.01%
Skin Reaction scored at (h)	24	48	24	48					24	48	24	48
No. reacted/No. Challenged	0/10	0/10	0/10	0/10					4/10	0/10	1/10	0/10

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Due to the lack of an inflammatory response at the 24 or 48 hour timepoints at both challenge and re-challenge, under the circumstances of this study AMP does not appear to be a sensitising agent.

Executive summary:

During the induction phase, the first injection at 1% and the second injection a t 0.5% of P-1826 (Group VIII) induced necrotic lesions, so the remaining eight injections were made with 0.1% solution. The 0.3% DNCB solution was necrotic for the entire 10 injections. At challenge with 0.05 and 0.01% P-1826 one animal in. Group VIII (test) showed mild skin reactions with 0.05%, but none of the animals in Group XI (negative control) showed any skin reactions a t 24 or at 48 hours. In the repeat challenge none of the animals in the test group (VIII) showed any reactions with .05 or 0.01% solution of P-1826, but in the negative control group (XI) four animals at 0.05% and one animal at 0.01% showed skin reactions at 24 h. A challenge with 0.3 and 0.03% DNCB solutions, induced skin reactions in the positive control group (X). The 0.03% solution did not elicite any skin reaction at 48 hour.