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Toxicological information

Skin sensitisation

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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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-Amino-2-methyl-1-propanol; AMP; P1826
- Lot/batch No.: 9B02-9B

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 topically treated with the solutions applied under an occlusive patch.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
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
Challengeopen allclose all
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).

Results and discussion

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, but was deemed not treatment-related via necropsy due to the presence of a lung infection.Eight of ten positive controls when challenged with DNCB at 24 hours showed skin reactions, and 3/10 showed reactions at 48 hours.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
2.5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 2.5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
2.5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2.5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.3%
No. with + reactions:
8
Total no. in group:
9
Clinical observations:
one animal died (not considered treatment related)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.3%. No with. + reactions: 8.0. Total no. in groups: 9.0. Clinical observations: one animal died (not considered treatment related).
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.3%
No. with + reactions:
8
Total no. in group:
9
Clinical observations:
one animal died (not considered treatment related)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.3%. No with. + reactions: 8.0. Total no. in groups: 9.0. Clinical observations: one animal died (not considered treatment related).
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:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 2.5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
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:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 2.5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
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:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
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:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5%. No with. + reactions: 2.0. Total no. in groups: 10.0.
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
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
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:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:

Any other information on results incl. tables

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

9a

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

8/9

3/9

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.


Applicant's summary and conclusion

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 9 animals and 3 out of 9 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.