Dimethyl(propyl)amine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

07 June - 21 June 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl(propyl)amine

EC Number:

213-139-9

EC Name:

Dimethyl(propyl)amine

Cas Number:

926-63-6

Molecular formula:

C5H13N

IUPAC Name:

dimethyl(propyl)amine

Specific details on test material used for the study:

- Lot/batch No.: K322/1

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain as cited in the study report: White New Zealand/Chbb:NZW (SPF)
- Source: Boehringer Ingelheim Pharma KG
- Age at study initiation: young adult animals
- Weight at study initiation: 4, 2.8, 2.9 kg
- Housing: single housing in stainless steel wire mesh cages with grating, floor area 3000 cm2
- Diet: Kliba-Labordiet (Klingenthalmuehle AG, Kaiseraugst, Switzerland), about 130 g per animal and day
- Water: 250 mL tap water per animal and day
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark/hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Remarks:

(24 hrs prior to testing)

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Amount applied: 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

14 days
Reading time points: 1, 24, 48 and 72 h, day 7 and day 14

Number of animals:

3 male animals

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap used: test patch (Idealbinde, Pfaelzische Verbandstoff-Fabrik, Kaiserslautern) and stretch (Fixomull adhesive fleece, Baiersdorf)

REMOVAL OF TEST SUBSTANCE
- Washing: after removal of the dressing, the application site was washed with Lutrol followed by Lutrol in water (1:1).
- Time after start of exposure: 4 hours

SCORING SYSTEM: Scoring was done as specified by the OECD guideline, according to the Draize scoring system.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: erythema grade 2 still was seen after 14 days.

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: erythema grade 1 still was seen after 14 days.

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: erythema grade 1 was seen at each of reading time points 1, 24, 48 and 72 hrs, with full reversibility reached at day 7.

Results 4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

2.2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: at day 14, 2/3 animals still showed erythema grade 1 and 2, respectively.

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: edema grade 1 still was seen at day 14.

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: edema grade 1 was seen at reading time points 48 h, 72 h, and at day 7 where it was accompanied by scaling. The finding was no more evident at day 14.

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Remarks on result:

other: this animal showed no edema at all.

Results 8

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0.6

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: 1/3 animals still showed edema grade 1 accompanied by scaling at day 14.

Irritant / corrosive response data:

Slight (1/3 animals) to moderate (2/3 animals) erythema was seen after 1 h. At 24 h, erythema became severe in one case and remained moderate and slight in the 2 other animals, respectively. At 48 and 72 h, 2/3 animals has severe erythema whereas the third animal still showed a slight effect. After 7 days, the two cases of severe erythema turned back to moderate whereas full reversibility was noticed for the third animal. After 14 days, one animal still showed moderate erythema whereas in the other one, the effect turned back to slight.
Regarding edema, whereas no effect was seen at reading time point 1 h, slight edema appeared in 1/3 animals at 24 h, and in 2/3 animals at 48 h. The effect in the 2 animals lasted until day 7 and was further accompanied by scaling. At day 14, only 1 of these 2 animals still showed edema with scaling.

Other effects:

scaling seen at day 7 (2/3 animals) and at day 14 (1/3).

Any other information on results incl. tables

Table 1: Details on findings and scores:

	Animal	Erythema  score	Edema  score
1h	1	2	0
	2	2	0
	3	1	0
24 hrs	1	3	1
	2	2	0
	3	1	0
48 hrs	1	3	1
	2	3	1
	3	1	0
72 hrs	1	3	1
	2	3	1
	3	1	0
7 d	1	2	1 + severe scaling
	2	2	1 + scaling
	3	0	0
14 d	1	2	1 + scaling
	2	1	0
	3	0	0

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

DMPA was tested for skin irritation in rabbits, under semi-occlusive conditions, according to the OECD TG 404 (1992). After 4 h exposure, the animals were observed during 14 days, with the skin being examined for signs of irritation at the following reading time points: 1, 24, 48 and 72 h, day 7 and day 14. The skin findings were assessed by scoring according to the Draize scoring system.
All 3 animals showed slight to severe erythema from 1 to 72 h; at day 7 and 14 slight to moderate erythema still was noticed in 2/3 animals, indicating that full reversibility was not reached at the end of the observation period of 14 days.
Slight edema appeared in 1/3 animals after 24 h and was seen in 2/3 animals at 48 h, 72 h and at day 7. At day 14, 1/3 animal still displayed slight edema. At 7 and 14 day, edema was accompanied by scaling.
Taking into account the mean erythema and edema scores obtained from all 3 animals over the reading time points 24, 48 and 72 h, and regarding the absence of full reversibility at day 14, the test item is to be considered as a skin irritant according to current evaluation criteria.