Registration Dossier

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:
1990
Report date:
1990

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of N-[3-(Dimethylamino)propyl]stearamide and N-[3-(Dimethylamino)propyl]hexadecan-1-amide
Molecular formula:
Not relevant
IUPAC Name:
Reaction mass of N-[3-(Dimethylamino)propyl]stearamide and N-[3-(Dimethylamino)propyl]hexadecan-1-amide
Test material form:
solid
Details on test material:
Test material: DMAPSA (Octadecanamide, N-(3-(dimethylamino)propyl)-) (CAS No. 7651-02-7).
Date of receipt: 24th July 1990.
Description: White waxy solid.
Storage: In original container at room temperature.
Specific details on test material used for the study:
Description: white waxy soìid
Container: plastic screw-top container
Sponsor's identification: DMAPSA
Date of arrival: 24 July 1990
Storage conditions: room temperature




Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12-16 weeks old
- Weight at study initiation: 2.42-2.62 kg
- Housing: The animals were individually housed in suspended metal cages.
- Diet and water (e.g. ad libitum): Free access to mains drinking water and food (Rabbit Diet, Preston Farmers Limited, New Leake, Boston, Lincolnshire, U.K. ) was allowed throughout the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-27
- Humidity (%): 64-73
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5g

VEHICLE
- Amount(s) applied: 0.5mL of distilled water

Duration of treatment / exposure:
4h
Observation period:
1, 24, 48, 72h and 7d
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsal/ flank area
- Type of wrap if used: 2.5cm x 2.5 cm gauze patch
The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked i n distiIIed water.
- Time after start of exposure: 4h after application

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : 1, 24, 48, 72h and 7d

SCORING SYSTEM:
- Method of calculation: scale of Draize J.H. (1959)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7d
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7d
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 3d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 3d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 3d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7d
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 7d
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7d
Irritant / corrosive response data:
Very sìight to well-defined erythema was noted at all treatment sites one to 48 hours after treatment. Well-defined erythema persisted at two treated skin sites at the 72-hour observation. L'ght brown scabbing at the remainìng treated skin site precluded evaluation of the skin responses at this time. At the 7-day observation no erythema was observed at the three treatment sites but incidents of hyperkerinisation and glossy skin were noted.
Very slight to slìght oedema was noted at two treated skin sites up to the 48 or 72-hour observations. Very slight to moderate oedema was noted at the remaining treatment site during the study but evaluation of oedema was not possible at the 72-hour observation time at this site due to other adverse dermal reactions.

Any other information on results incl. tables

Individual scores are provided below for skin irritation

 

Observation time

Rabbit 1 (male)

Rabbit 2 (male)

Rabbit 3 (male)

Eythema formation

1h

1

2

2

24h

2

2

2

48h

2

2

2

72h

2

2

? eSp

7d

0 Hy

 0 Hy

0 Gl

Oedema formation

1h

1

1

1

24h

2

2

3

48h

1

2

2

72h

0

1

?0d

7d

0

0

0

Hy = possible hyperkeratinisation

Sp = scab appears restricted to skin surface

Od = well-defined oedema

GL = glossy skin

?e = presence of adverse dermal reactions precludes macroscopic observation of erythema

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test material DMAPSA, was classified as a moderate irritant to rabbit skin. No corrosive effects were noted.
The test material was also classified as 'irritant according to EEC Iabelìing regulations. The symbol "Xi" and risk phrase R 38 "IRRITATING TO SKIN" are requìred.
Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals

(1981) No. 404 "Acute Dermal Irritation/Corrosion" referenced as Method B4 in Commission Directive 84/449/EEC. The results may be used as a basis for classification and labelling under Commission Directive 83/467/EEC and the U.K. Approved Code of Practice "Classification and Labelling of Substances Dangerous for Supply".

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined erythema, well-defined to moderate oedema, hyperkeratinisation, hardened light brown scab and glossy skin. In one animal adverse dermal reactions precluded macroscopic observation of erythema and oedema at the 72 -hour observation.

The test material DMAPSA, was classified as a moderate irritant to rabbit skin. No corrosive effects were noted.

The test material was also classified as 'irritant according to EEC Iabelìing regulations. The symbol "Xi" and risk phrase R 38 "IRRITATING TO SKIN" are requìred.