N,N,4-trimethylpiperazine-1-ethylamine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-03-05 to 2003-03-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Commission Directive 92/69/EEC, 8.4: (Acute Toxicity - Skin Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: (MAFF); July 2000

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N,N,4-trimethylpiperazine-1-ethylamine

EC Number:

203-183-7

EC Name:

N,N,4-trimethylpiperazine-1-ethylamine

Cas Number:

104-19-8

Molecular formula:

C9H21N3

IUPAC Name:

dimethyl[2-(4-methylpiperazin-1-yl)ethyl]amine

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 922601
- Expiration date of the lot/batch: 2003-12-12
- Purity test date: Not indicated by the sponsor; treated as 100% pure


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability under test conditions: Not indicated


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
The test substance was applied undiluted as delivered by the sponsor.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 1.883 grams
- Housing: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm)
- Diet (e.g. ad libitum): Standard laboratory rabbit diet
- Water (e.g. ad libitum): Free access to tap-water.
- Acclimation period: at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3°C
- Humidity (%): 30-70%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours dark per day

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): 0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

no details available, only 1 h

Number of animals:

1 animal

Details on study design:

TEST SITE
- Area of exposure: 2x3 cm
- % coverage: approximately 150 square centimeters
- Type of wrap if used: Metalline patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After each removal of a dressing, the treated skin was cleaned of residual test substance using water
- Time after start of exposure: 1 hour

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) - approximately one hour after removal of patches and 24, 48 and 72 hours later

SCORING SYSTEM:
- Method of calculation: The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:

Erythema and eschar formation:
No erythema - 0
Very slight erythema (barely perceptible) - 1
Well-defined erythema - 2
Moderate to severe erythema - 3
Severe erythema (beet redness) - 4

Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema (= 4) is given.
Oedema formation:
No oedema - 0
Very slight oedema (barely perceptible) - 1
Slight oedema (edges of area well-defined by definite raising) - 2
Moderate oedema (raised approximately 1 millimeter) - 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) - 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

3min treatment site

Time point:

other: immediately

Score:

3

Max. score:

4

Reversibility:

not reversible

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

3 min treatment site

Time point:

other: immediately

Score:

1

Max. score:

4

Reversibility:

not reversible

Results 3

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

3 min treatment site

Time point:

other: 1 hour

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: grey discoloration, a sign of necrosis (superficial)

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

3 min treatment site

Time point:

other: 1 hour

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: grey discoloration, a sign of necrosis (superficial)

Results 5

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

1 hour and intended 4-hours treatment site

Time point:

other: immediately

Score:

4

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: wound with serious exudate on the edges of the treatment site; grey discoloration, a sign of necrosis (superficial)

Results 6

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

1 hour and 4 hours treatment site

Time point:

other:

Score:

1

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: wound with serious exudate on the edges of the treatment site; grey discoloration, a sign of necrosis (superficial)

Irritant / corrosive response data:

Three minutes of exposure to 0.5 ml resulted moderate to severe erythema and very slight oedema immediately after removal of the bandage. One hour of exposure on the designated 1 and 4 hours treatment sites resulted in severe erythema/necrosis and very slight oedema and in the treated skin-areas of the rabbit. A wound with serous exudate on the edges of the treatment site was observed on both the 1-hour and intended 4-hours treatment site.
Simultaneous scoring of the 3-minutes treatment site showed severe erythema/necrosis and very slight oedema 1 hour after removal of the bandage.

Other effects:

- Other adverse local effects:
No staining of the treated skin by the test substance was observed

- Other adverse systemic effects:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred

Applicant's summary and conclusion

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

Based on the results and according to the CLP Regulation, the substance is classified as corrosive to skin (Skin Corrosive 1B).