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Toxicological information

Skin irritation / corrosion

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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
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:
N,N-dimethylpropan-2-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

Resultsopen allclose all
Irritation parameter:
other: corrosion
Basis:
mean
Remarks:
(2 animals)
Remarks on result:
other: Full thickness necrosis occurred after a 3 min exposure period.
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
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.