N,N-dimethylisopropylamine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

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:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dimethylisopropylamine

EC Number:

213-635-5

EC Name:

N,N-dimethylisopropylamine

Cas Number:

996-35-0

Molecular formula:

C5H13N

IUPAC Name:

dimethyl(propan-2-yl)amine

Details on test material:

- Name of test material (as cited in study report): N,N-Dimethylisopropylamine
- Analytical purity: 99.773 %
- Lot/batch No.: B 2009 13.03.06 13:30
- Substance number: 06/0180-1

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Centre Lago S. A., 01540 Vonnas, France
- Age at study initiation: ca. 6 months
- Weight range at study initiation: 3.43 kg – 3.52 kg
- Housing: single housing
- Diet: Kliba-Labordiaet (Kaninchen & Meerschweinchenhaltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 5 days before application


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Air changes (per hr): The animals were housed in fully air-conditioned rooms.
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated skin sites of the same animal.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test patch (2.5 cm x 2.5 cm) was moistened with a dose of 0.5 mL of the undiluted liquid test substance.

Duration of treatment / exposure:

3 min

Observation period:

14 days
(A check for dead or moribund animals was made twice each workday and once daily at weekends.)

Number of animals:

2

Details on study design:

TEST SITE
- Area of exposure: 2.5x2.5 cm


REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test substance was removed at the end of the exposure period with Lutrol and Lutrol/water (1:1).
- Time after start of exposure: 3 min

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

other: corrosion

Basis:

mean

Remarks:

(2 animals)

Remarks on result:

other: Full thickness necrosis occurred after a 3 min exposure period.

Results 2

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(2 animals)

Time point:

other: 24, 48 and 72 h

Score:

3.3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 3

Irritation parameter:

edema score

Basis:

mean

Remarks:

(2 animals)

Time point:

other: 24, 48 h and 72 h

Score:

2.2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Any other information on results incl. tables

Mean erythema score after 24, 48 and 72 h; (animal1/animal2)

	24 h	48 h	72 h	mean
3 min	3/3	3/4	3/4	3/3.7

Mean edema score after 24, 48 and 72 h; (animal1/animal2)

	24 h	48 h	72 h	mean
3 min	2/3	2/2	2/2	2/2.3

Moderate to severe erythema (grade 2-4) and moderate to marked edema (grade 2-3), partly extended beyond the area of exposure, were observed in all animals immediately after removal of the patch up to study termination on day 14.

Additional findings like scaling, severe scaling, petechiae, eczematoid skin change and thickening of the skin at the application area were noted over the observation period. The skin of the application area appeared temporarily whitish-brownish, slightly brownish or dark brown. The cutaneous reactions were not reversible in the animals within 14 days after removal of the patch. The first animal still showed erythema, edema, severe scaling, eczematoid skin change and thickening of the skin at study termination. The skin was soft and relocatable. In the second animal erythema, edema, eczematoid skin change and thickening of the skin were noted and the skin appeared dark brown.

Pathological-anatonomical evaluation:

Animal 02 (right flank): lesion at the application area, incrusted surface.

Histopathological examination:

Animal 02 (right flank): full thickness necrosis of epidermis with severe, diffuse intraepidermal infiltration with lymphocytes, histiocytes, neutrophilic and eosionophilic granulocytes and serocellular crusts.

Major finding: Full thickness necrosis occurred after a 3 min exposure period.

Applicant's summary and conclusion

Interpretation of results:

Category 1A (corrosive) based on GHS criteria

Conclusions:

Under the experimental conditions, DMIPA was considered as corrosive when applied topically to rabbits

Executive summary:

The acute dermal irritation of N,N-dimethylisopropylamine (DMIPA) was evaluated in rabbits according to OECD 404 guideline. DMIPA was applied undiluted to the skin of 2 New-Zealand White albino rabbits and held in contact for 3 minutes by means of a semi-occlusive dressing. Mean scores over 24, 48 and 72 hours for each animal were for erythema and for oedema. Animals were then observed daily during 14 days. Moderate to severe erythema (grade 2-4) and moderate to marked oedema (grade 2-3), partly extended beyond the area of exposure, were observed in all animals immediately after removal of the patch up to study termination on day 14. Additional findings like scaling, severe scaling, petechiae, eczematoid skin change and thickening of the skin at the application area were noted over the observation period. The skin of the application area appeared temporarily whitish-brownish, slightly brownish or dark brown. The cutaneous reactions were not reversible in the animals within 14 days after removal of the patch. The first animal still showed erythema, oedema, severe scaling, eczematoid skin change and thickening of the skin at study termination. The skin was soft and relocatable. In the second animal erythema, edema, eczematoid skin change and thickening of the skin were noted and the skin appeared dark brown.

Under the experimental conditions, DMIPA was considered as corrosive when applied topically to rabbits.