N,N,4-trimethylpiperazine-1-ethylamine

Endpoint summary

Description of key information

Skin irritation: A key primary skin irritation/corrosion study in rabbit is available. Based on the results, the substance is considered corrosive to the skin.

Eye irritation: no key study is available for this endpoint

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Reference 2

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: (MAFF); July 2000

Deviations:

no

GLP compliance:

yes

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.

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

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

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

3min treatment site

Time point:

other: immediately

Score:

3

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

3 min treatment site

Time point:

other: immediately

Score:

1

Max. score:

4

Reversibility:

not reversible

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)

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)

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)

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

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).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)

Reference 2

Endpoint:

eye irritation: in vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin corrosion/irritation in vivo:

A key primary skin irritation/corrosion study with the test substance in the rabbit is available. This study was carried out according to OECD guideline 404. One rabbit was exposed to three samples of 0.5 mL of test substance applied to separate skin-sites on intact, clipped skin using a semi-occlusive dressing. The exposure periods were 3 minutes and 1 hour. Observations were made on all visible application sites immediately after removal of the bandages.

Three minutes of exposure to the test substance resulted in moderate to severe erythema and very slight edema 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 edema in the treated skin areas of the rabbit. A wound with serious 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 edema 1 hour after removal of the bandage.

Based on the results of the study, the observations were visible within 1 hour after a 3 minutes exposure period. This leads to a classification as skin corrosive category 1A according to CLP Regulation.

Skin irritation in vitro: no key in vitro skin irritation study is required as adequate in vivo data is available

Eye irritation: no key study is required as the substance is demonstrated to be corrosive to the skin.

Justification for classification or non-classification

The study is demonstrated to be corrosive to the skin and is thus classified as category 1A skin corrosive according to CLP Regulation.

Therefore, the substance is also classified as serious eye damage category 1.