2-amino-2-methylpropanol

Endpoint summary

Description of key information

Skin sensitisation/animals:

2 studies on the skin sensitising potential of AMP are available. In the first study Guinea pigs were treated topically with 0.5 mL of a 10% AMP solution; after 24 hours, sites were cleaned and scored for erythema and edema according to the method of Draize (Parekh, 1982a). 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. Sites were scored again at 3 and 48 hours. Following challenge with 2.5% and 5% solutions of AMP, none of the animals exhibited a positive response.

In a second study of very similar design (0.05 mL of a 1% AMP solution for inductions, 0.1mL of 0.05% and 0.01% for challenge), guinea pigs were subjected to intradermal injections during the induction and challenge phases (Parekh, 1982b). During the induction phase, the first injection at 1% and second injection at 0.5% AMP induced necrotic lesions, so the remaining 8 injections were made with 0.1% solutions. At challenge with 0.05% and 0.01% AMP, one animal in the test group showed mild reactions with 0.05%. In a repeat challenge, none of the animals in the test group showed any reactions with AMP, so the material was considered to be non-sensitizing following intradermal application.

Two adequate skin sensitization tests have been conducted in guinea pigs, topically and intradermally. Results from both tests indicate that AMP has no sensitization potential.

Human data (section 7.10.4):

Cipolla et al (1997) reported two cases of airborne skin dermatitis in a cosmetic factory using AMP-100. Patch testing in exposed workers and control workers evidenced that these skin reactions were skin irritation and not skin sensitisation, because they only occured at high test concentrations (>=10% AMP in water or ethanol) and because pre-exsisting exposure to AMP did not lead to significantly worse skin reactions.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

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

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.

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.

Route:

intradermal

Vehicle:

water

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

Route:

intradermal

Vehicle:

water

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)

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.

Remarks on result:

no indication of skin sensitisation

Remarks:

detailed results are provided in below section

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

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.

Reference 2

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

Buehler test (Patch-Test)

GLP compliance:

no

Type of study:

Buehler test

Justification for non-LLNA method:

LLNA test not available at the time of testing. Buehler test considered to be adequate data

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 topically treated with the solutions applied under an occlusive patch.

Concentration / amount:

Induction- 0.5ml of 10% (two doses) and 5% (remaining 8 doses) P-1826 solution Challenge- 0.5ml of 2.5% and 5% solutions of P-1826

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

Induction- 0.5ml of 10% (two doses) and 5% (remaining 8 doses) P-1826 solution Challenge- 0.5ml of 2.5% and 5% solutions of P-1826

No. of animals per dose:

10

Details on study design:

One group was treated with 0.5mL of 10% 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, the patches were removed, and sites were cleaned and scored at 24 and 48 hours 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 0.5mL of 2.5% and 5% solutions of P-1826. Positive and negative control animals were also challenged with 0.3% DNCB solution. After 24 hours, the test material was cleaned away, 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.

Challenge controls:

Positive and negative control animals were challenged with 0.3% dinitrochlorobenzene (DNCB) solution.

Positive control substance(s):

yes

Remarks:

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

Positive control results:

During the induction, the positive control, DNCB, elicited a mild to strong reaction during the 10 applications. There was one death in the positive control group on day 6, but was deemed not treatment-related via necropsy due to the presence of a lung infection.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.3%

No. with + reactions:

8

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

0.3%

No. with + reactions:

8

Total no. in group:

10

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

5%

No. with + reactions:

2

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

other: negative control (DCNB)

Dose level:

0.3%

No. with + reactions:

4

Total no. in group:

10

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

other: negative control (DCNB)

Dose level:

0.3%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

During the induction, the 10% P-1826 solution was found to be mildly irritating to all animals in the test group, so the remaining 8 doses during the induction were made with a 5% solution. 

 

The report only contains a summary of the results. This reproduced here:

 

 

Group II TEST

Group VI Positive Control

Group VIII Negative Control

Material

P-1826 (AMP)

DCNB

Saline

No. of animals

10

9^a

10

Induction dose

10% (2 doses), 5% (8 doses)

0.3%

N/A

Challenge material

P-1826 (AMP)

DCNB

P-1826 (AMP)

DCNB

Challenge Dose or conc.

2.5%

5%

0.3%

2.5%

5%

0.3%

Time of skin reaction scoring

24

48

24

48

24

48

24

48

24

48

24

48

No. reacted/No. Challenged

0/10

0/10

0/10

0/10

8/10

3/10

0/10

0/10

0/10

2/10

4/10

0/10

^a One animal died during the study of an unrelated lung infection

 

At challenge with 2.5% and 5% solutions of P-1826, none of the animals in the test or negative control groups showed any skin reactions at 24 hours, but the positive control animals showed mild skin reactions at 48 hours.

 

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

2-Amino-2-methyl-1-propanol was a non-sensitizer in the topical sensitization test in guinea pigs, under these test conditions.

Executive summary:

A standard Buehler assay was conducted on AMP using 30 male guinnea pigs. The animals were separated into 3 groups of 10 animals, a test group,a negative and positive control group. In the Induction phase of the study, the shaved backs and flanks of the test group were exposed to the test compound at a concentration of 10% for 24 hours under an occlusive dressing. At the end of this exposure period the test sites were cleaned and scored for irritation at 24 and 48 hours after exposure. At 48 hours, after the reading of skin irritation, the process was repeated until a total of 10 exposures had occurred. Due to the irritation (mild) caused by 10% test compound the 3rd through to the 10th exposures were done using a 5% concentration.

The positive and negative control groups followed the same procedure, but the animals were exposed to a 0.3% solution of Dinitrochlorobenzene (DNCB) or saline solution respectively.

At the Challenge phase, the test animals and the negative control animals were exposed for 24 hours to 2.5 and 5% test material at 2 previously untreated sites under an occlusive patch. After 24 hours the sites were cleaned and scored for signs of erythema and edema. The sites were scored again at 48 hours. The positive control group and the negative control group were challenged in the same way using a 0.3% concentration of DNCB.

One of the positive control group died during the study due to a lung infection. There were no other mortalities or signs of systemic toxicity observed. In the Test group, at both 24 and 48 hours there was no evidence of inflammation indicative of a sensitising response. In the positive control group 8 out of 10 animals and 3 out of 10 animals gave a positive response at 24 and 48 hours indicating that the positive control worked and that the study is valid. In the negative control group, there was no evidence of irritation or inflammation at the sites treated with the test compound. At 24 hours, 4 out of 10 animals displayed irritation following treatment with DNCB, this irritation had cleared at 48 hours.

 

Under the circumstances of this study, AMP does not appear to be a skin sensitiser.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Considering the lack of skin sensitising potential and its low vapour pressure, it is unlikely that AMP would be a respiratory sensitiser.

Justification for classification or non-classification

Based on the negative studies available for AMP it does not meet the requirements for classification as a skin sensitising agent.