N,N-dimethyl-N'-(2,2,6,6-tetramethylpiperidin-4-yl)propane-1,3-diamine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May - Dec 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dimethyl-N'-(2,2,6,6-tetramethylpiperidin-4-yl)propane-1,3-diamine

EC Number:

278-817-9

EC Name:

N,N-dimethyl-N'-(2,2,6,6-tetramethylpiperidin-4-yl)propane-1,3-diamine

Cas Number:

78014-16-1

Molecular formula:

C14H31N3

IUPAC Name:

N-[3-(dimethylamino)propyl]-2,2,6,6-tetramethylpiperidin-4-amine

Test material form:

other: liquid

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Age at study initiation: 1st and 2nd pre-test: 9 - 10 weeks (beginning of treatment); main study: 10 – 11 weeks (beginning of treatment)
- Weight at study initiation:1st and 2nd pre-test: 19.3-19.7 g and 19.9-21-1 g (beginning of treatment); main study: 18.6-23.3 g (beginning of treatment)
- Housing: In groups of 4 (pre-test) and 5 (main study)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-2°C°C
- Humidity (%): 45-65%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 30 May 2012 To: 27 June 2012

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

0.5, 1 and 2.5%

No. of animals per dose:

5

Details on study design:

A solubility experiment demonstrated that test item solutions at different concentration could be prepared using acetone:olive oil (4+1 v/v) as vehicle.
Due to the corrosive properties of the test item, test item concentrations of 5 and 10% (w/w) were initially tested in one animal, each, in the pre-experiment. Both animals tested, developed an erythema of the ear skin. The animal treated with a concentration of 5% developed a very slight erythema (score 1) on days 3 and 4. The animal treated with the high dose (10%) developed a slight to well visible erythema (score 1 on days 2, 5 and 6; score 2 on days 3 and 4) and a visible swelling of the ears on day 6. Moreover, the animal developed an increase in ear thickness in 54% compared to pre-treatment value. On day 3 both animals developed signs of systemic toxicity, as indicated by a hunched posture and reduced spontaneous activity.
Therefore, a second pre-test was performed using test item concentrations of 1 and 2.5% (w/w). These animals showed no signs of systemic toxicity or excessive local skin irritation.
Thus, the test item in the main study was assayed at 0.5, 1, and 2.5% (w/w).

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

The periodic positive control experiment was performed with alpha-Hexyl cinnamaldehyde in acetone:olive oil (4+1 v/v) using CBA/CaOlaHsd mice in April 2012.

In vivo (LLNA)

Results

Results 1

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Vehicle Control Group (acetone:olive oil (4+1 v/v)): 874 0.5% test item: 786 1% test item: 854 2.5% test item: 2149

Results 2

Key result

Parameter:

SI

Value:

0.9

Test group / Remarks:

0.5% test item in acetone:olive oil (4+1 v/v)

Results 3

Key result

Parameter:

SI

Value:

0.98

Test group / Remarks:

1% test item in acetone:olive oil (4+1 v/v)

Results 4

Key result

Parameter:

SI

Value:

2.46

Test group / Remarks:

2.5% test item in acetone:olive oil (4+1 v/v)

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

The test item was not a skin sensitiser under the test conditions of this study.

Executive summary:

In the study the test item TAT (Triacetonetriamine) dissolved in acetone:olive oil (4+1 v/v) was assessed for its possible skin sensitising potential.

For this purpose a local lymph node assay was performed using test item concentrations of 0.5, 1, and 2.5% (w/w). The highest concentration tested was the highest concentration that could be achieved whilst avoiding systemic toxicity and excessive local skin irritation as confirmed by a pre-experiment.

The animals did not show any signs of systemic toxicity or local skin irritation during the course of the study and no cases of mortality were observed. In this study Stimulation Indices (S.I.) of 0.9, 0.98 and 2.46 were determined with the test item at concentrations of 0.5, 1, and 2.5% (w/w) in acetone:olive oil (4+1 v/v), respectively.

The test item TAT (Triacetonetriamine) was not a skin sensitiser under the test conditions of this study.