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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:
weight of evidence
Study period:
30 Mar - 13 May 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
- limited documentation
GLP compliance:
no
Type of study:
Buehler test
Justification for non-LLNA method:
This study was already availabe before the LLNA method became available.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-Dimethylamino-2-methyl-1-propanol or 73% DMAMP or Polymeen(TM)A (P-2614)
- Analytical purity: 72.03%
- Lot No.: 730H18DF36
- pH: 12.5
Specific details on test material used for the study:
- Lot No. 73 0H18DF3 6
- 2-Dimethylamino-2-methyl-1-propanol, 72.03%
- APHA (color) 15
- pH 12.5
- Sp. Gr. 0.947
- Made from DMAMP 80 Lot No. OH18DF36

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Murphy Breeding Laboratories, Inc., Plainfield, Illinois, USA
- Age at study initiation: at least 4 weeks
- Weight at study initiation: 250 - 300 g
- Housing: 5 per cage
- Diet (e.g. ad libitum): Purina Guinea Pig Chow #5026, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least one week

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
induction:
group VI (treatment group): 0.5 mL of a 0.5% solution of DMAMP in saline
group IV (positive control group): 0.5 mL of 0.3% dinitrochlorobenzene solution (DNCB, solubilised in a minimum volume of alcohol and made to volume with saline)
group X and XI (negative control groups): 0.5 mL of saline

challenge:
group VI (treatment group): 0.5 mL of a 0.25% and a 0.5% solution of DMAMP
group IV (positive control group): 0.5 mL of 0.03% and 0.3% dinitrochlorobenzene solution (DNCB, solubilised in acetone instead of alcohol)
group X (negative control group for DMAMP): 0.5 mL of a 0.25% and a 0.5% solution of DMAMP
group XI (negative control group for DNCB): 0.5 mL of 0.3% dinitrochlorobenzene solution (DNCB, solubilised in acetone instead of alcohol)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
induction:
group VI (treatment group): 0.5 mL of a 0.5% solution of DMAMP in saline
group IV (positive control group): 0.5 mL of 0.3% dinitrochlorobenzene solution (DNCB, solubilised in a minimum volume of alcohol and made to volume with saline)
group X and XI (negative control groups): 0.5 mL of saline

challenge:
group VI (treatment group): 0.5 mL of a 0.25% and a 0.5% solution of DMAMP
group IV (positive control group): 0.5 mL of 0.03% and 0.3% dinitrochlorobenzene solution (DNCB, solubilised in acetone instead of alcohol)
group X (negative control group for DMAMP): 0.5 mL of a 0.25% and a 0.5% solution of DMAMP
group XI (negative control group for DNCB): 0.5 mL of 0.3% dinitrochlorobenzene solution (DNCB, solubilised in acetone instead of alcohol)
No. of animals per dose:
40 (10 per group)
Details on study design:
RANGE FINDING TESTS: In the initial test, a 0.5% solution of DMAMP was least irritating. Therefore, this concentration was used for the topical applications.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Exposure period: ca. 3 weeks
- Test groups: 1
- Control group: 1 positive control group, 2 negative control groups
- Site: the animals´ backs and flanks (shaved free of hair)
- Frequency of applications: 2 to 3 times a week
- Duration: 24 h
- Concentrations: 0.5% solution of DMAMP

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1 day (24 h)
- Exposure period: 1 day
- Test groups: 1
- Control group: 1 positive control group, 2 skin irritation control groups
- Site: the animals´ backs and flanks
- Concentrations: 0.25 and 0.5% solution of DMAMP
- Evaluation (hr after challenge): 24 and 48 h (actually 27 and 51 h)

OTHER:
Induction period:
After 24 h exposure the patches were removed, the treated skin sites cleaned and scored at 24 and 48 h for erythema and edema according to Draize.
At 48 h the topical application procedure was repeated with each group of animals two to three times a week until a total of 10 applications have been made. After the last application, the animals were allowed to rest for two weeks.
Challenge:
After 24 h exposure, the patches were removed and the challenge sites were depilated with "Nair" (a hair removal product with the active ingredients: calcium hydroxide and sodium hydroxide). 3 h after removal of the hair, the challenge sites were scored for inflammatory skin reactions (erythema and edema) according to Draize. Theses sites were scored again at 48 h (24 h after the first scoring).

Challenge controls:
Negative control groups:
group X: negative control group for DMAMP
group XI: negative control group for DNCB
Positive control substance(s):
yes
Remarks:
induction: 0.3% solution of dinitrochlorobenzene (DNCB) in alcohol:saline (20:80); challenge: 0.03% and 0.3% solution of dinitrochlorobenzene (DNCB) in acetone instead of alcohol

Results and discussion

Positive control results:
Positive control responded as expected with a clear sensitising response at 24 h (7 of 10 animals) and 48 hours (8 of 10 animals) for a 0.3% solution of dinitrochlorobenzene. A solution of 0.03% dinitrochlorobenzene showed a decreased sensitising response: at 24 h (4 of 10 animals) and 48 hours (6 of 10 animals).

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.25%
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: 0.25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.25%
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.25%. No with. + reactions: 2.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.5%
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5%. No with. + reactions: 1.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.5%
No. with + reactions:
4
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5%. No with. + reactions: 4.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.03%
No. with + reactions:
4
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.03%. No with. + reactions: 4.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.03%
No. with + reactions:
6
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.03%. No with. + reactions: 6.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.3%
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.3%. No with. + reactions: 7.0. Total no. in groups: 10.0.
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
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: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.25%
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Remarks:
negative control for DMAMP
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.25%
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.5%
No. with + reactions:
6
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.5%
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.3%
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.3%
No. with + reactions:
1
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 period (initial ten applications), the animals in the test group and in the positive control group showed mild skin reactions. When challenged with 0.25% of DMAMP, two animals in the test group showed skin reactions at 48 h and 7 animals in the negative control group for DMAMP at 24 h as well as at 48 h. A solution of 0.5% of DMAMP also led to skin reactions in more animals of the negative control group of DMAMP (6 of 10) than of the test group (1 of 10) at the 24 h scoring. Also at the second reading more animals of the negative control group (7/10) than of the test group (4/10) showed skin reactions. At challenge with 0.3% dinitrochlorobenzene (DNCB) solution, the positive control gave a valid response.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
2-Dimethylamino-2-methyl-1-propanol was a nonsensitizer under the conditions of this test. The positive control DNCB gave an expected positive response.